Stilbene and Fused Stilbene Derivatives as Solar Cell Dyes

ABSTRACT

The present application discloses stilbene derivative compounds and phenylbenzofuran compositions, useful in the manufacture of dye-sensitized solar cells and other similar technology.

TECHNICAL FIELD

The present invention is in the field of material compositions used toassemble dye sensitized solar cells (DSSC) and other dye sensitizedelectronic devices such as information storage devices, sensing devicesand imaging devices. In particular, it concerns the utility of novelorganic chromophores as the sensitizing dyes in dye sensitizedelectronic devices.

BACKGROUND

Sensitization of semiconductor solids such as metal oxides in imagingdevices, memories, sensors, and solar cells can serve as an effectivemeans of energy transduction. These devices use metal oxides, such astitanium dioxide that are transparent to light but can be sensitized tothe desired spectrum through the use of sensitizing agents that absorblight energy and transduce it into electrical power or an electricalsignal. This sensitization occurs through charge injection into themetal oxide from the excited state of the dye sensitizer. Sensitizerssuch as transition metal complexes, inorganic colloids and organic dyemolecules are used.

Prominent among such technologies is the dye-sensitized metal oxidesolar cell (DSSC). DSSCs use a dye to absorb light and initiate a rapidelectron transfer to a nanostructured oxide such as TiO₂. The mesoscopicstructure of the TiO₂ allows building of thick, nanoporous films withactive-layer thicknesses of several microns. The dye is then adsorbed onthe large surface area of the mesoporous TiO₂. Charge balance andtransport is achieved by a layer having a REDOX couple, such asiodide/triiodide, Co(II)/Co(III) complexes, and Cu(I)/Cu(II) complexes.

Dyes based on transition metal complexes are disclosed in Gratzel etal., U.S. Pat. Nos. 4,927,721 and 5,350,644. These dye materials aredisposed on mesoporous metal oxides that have a high surface area onwhich the absorbing, sensitizing layer can be formed. This results in ahigh absorptivity of light in the cell. Dyes such as Ru(II)(2,2′-bipyridyl 4,4′ dicarboxylate)₂ (NCS)₂ have been found to beefficient sensitizers and can be attached to the metal oxide solidthrough carboxyl or phosphonate groups on the periphery of thecompounds. However, when transition metal ruthenium complexes are usedas sensitizers they must be applied to the mesoporous metal oxide layersin a coat as thick as 10 micrometers or thicker in order to absorbenough solar radiation to attain sufficient power conversionefficiencies. Further, the ruthenium complexes are expensive. Inaddition, such dyes must be applied using volatile organic solvents,co-solvents, and diluents because they are not dispersible in water.Volatile organic compounds (VOCs) are significant pollutants that canaffect the environment and human health. While VOCs are usually notacutely toxic, they may have chronic health and environmental effects.For this reason, governments around the world are seeking to reduce thelevels of VOCs.

One type of dye-sensitized solar cell is known as the Gratzel cell.Hamann et al., “Advancing beyond current generation dye-sensitized solarcells,” (the disclosure of which is incorporated in its entirety byreference, hereinafter “Hamann”) describes the Gratzel cell. The Gratzelcell includes crystalline titanium dioxide nanoparticles serving as aphotoanode in the photovoltaic cell. The titanium dioxide is coated withlight sensitive dyes. The titanium dioxide photoanode includes 10-20 nmdiameter titanium dioxide particles forming a 12 μm transparent film.The 12 μm titanium dioxide film is made by sintering the 10-20 nmdiameter titanium dioxide particles so that they have a high surfacearea. The titanium dioxide photoanode also includes a 4 μm film oftitanium dioxide particles having a diameter of about 400 nm. The coatedtitanium dioxide films are located between two transparent conductingoxide (TCO) electrodes. Also disposed between the two TCO electrodes isan electrolyte with a redox shuttle.

The Gratzel cell may be made by first constructing a top portion. Thetop portion may be constructed by depositing fluorine-doped tin dioxide(SnO.sub.2F) on a transparent plate, which is usually glass. A thinlayer of titanium dioxide (TiO₂) is deposited on the transparent platehaving a conductive coating. The TiO₂ coated plate is then dipped into aphotosensitized dye such as ruthenium-polypyridine dye in solution. Athin layer of the dye covalently bonds to the surface of the titaniumdioxide. A bottom portion of the Gratzel cell is made from a conductiveplate coated with platinum metal. The top portion and the bottom portionare then joined and sealed. The electrolyte, such as iodide-triiodide,is then typically inserted between the top and bottom portions of theGratzel cell.

Typically, thin films for Dye Sensitized Solar Cells (DSSC) are composedof a single metal oxide—usually titanium dioxide, which in addition tonanoparticles, may be utilized in the form of larger 200 to 400 nm scaleparticles or as dispersed nanoparticles formed in-situ from a titaniumalkoxide solution. In one embodiment, the present application disclosesthe use of multiple morphologies of titanium oxide as well as othermetal oxides, which provide a boost in efficiency over the single metaloxide system. The additional metal oxides that may be employed include,but are not limited to, alpha aluminum oxide, gamma aluminum oxide,fumed silica, silica, diatomaceous earth, aluminum titanate,hydroxyapatite, calcium phosphate and iron titanate; and mixturesthereof. These materials may be utilized in conjunction with traditionaltitanium oxide thin films or with a thin film dye sensitized solar cellsystem as described in U.S. Provisional Patent Application No.61/237,137, filed Aug. 26, 2009, entitled “Low Cost Thin Film for DyeSensitized Solar Cells,” the disclosure of which is incorporated hereinby reference in its entirety.

In operation, the dye absorbs sunlight, which results in the dyemolecules becoming excited and transmitting electrons into the titaniumdioxide. The titanium dioxide accepts the energized electrons, whichtravel to a first TCO electrode. Concurrently, the second TCO electrodeserves as a counter electrode, which uses a redox couple such asiodide-triiodide (I₃—/I—) to regenerate the dye. If the dye molecule isnot reduced back to its original state, the oxidized dye moleculedecomposes. As the dye-sensitized solar cell undergoes a large number ofthe oxidation-reduction cycles in the lifetime of operation, more andmore dye molecules undergo decomposition over time, and the cell energyconversion efficiency decreases.

Hattori and his coworkers (S. Hattori, Y. Wada, S. Yanagida and S.Fukuzumi, J. Am. Chem. Soc., 2005, 127, 9648) have used copper (I/II)redox couples in DSSCs using ruthenium-based dyes, with very lowresulting efficiencies. Peng Wang and his coworkers improved theperformance of copper redox-based dye DSSCs using an organic dye (YuBai, Qingjiang Yu, Ning Cai, Yinghui Wang, Min Zhang and Peng Wang,Chem. Commun., 2011, 47, 4376-4378). The voltage generated from suchcells far exceeded voltage generated by any iodide/triiodide based redoxcouple.

SUMMARY OF THE INVENTION

A dye sensitized solar cell (DSSC) is a low-cost solar cell, often athin film solar cell. The present application discloses high efficientdye sensitized solar cells, and solar cell dyes for use in such DSSCs.In a particular embodiment, the solar cell is based on a semiconductorthat is formed between a photo-sensitized anode and an electrode.

Described here is a solar cell dye for use in a DSSC, wherein the dye isa compound of formula I:

wherein R⁶ is selected from the group consisting of —NR³R⁴, —R³, —OR³and halo; R⁵ is —(CR═CR—)_(n)(CR═CR²—)R¹; n is an integer from 0 to 10,R¹ and R² are independently selected from the group consisting of —H,—CN, —COOR, CONHR, CON(H)OR, —SO₃R, —SO₂R—OSO₃R, —PO₃H R, and —OPO₃H R,further wherein at least one of R¹ and R² is not —H; each R isindependently selected from —H and C₁₋₆ linear or branched alkyl; and R³and R⁴ are independently selected from the group consisting of H,substituted or unsubstituted linear or branched C₁-C₁₀ alkyl,substituted or unsubstituted phenyl, substituted or unsubstituted C₆-C₁₀aryl, substituted or unsubstituted C₅-C₁₀ heteroaryl, substituted orunsubstituted C₅-C₁₀ cycloalkyl, and substituted or unsubstituted C₅-C₁₀heterocycloalkyl; or R³ and R⁴ attached to their N together form a ringthat is substituted or unsubstituted C₅-C₁₀ heterocycloalkyl,

Also described herein is a solar cell dye for use in a DSSC, wherein thedye is a compound of formula V:

wherein either R⁶ is selected from the group consisting of —NR³R⁴, —R³,—OR³ and halo, and R⁵ is —(CR═CR—)_(n)(CR═CR²—)_(m)R¹; or R⁶ is—(CR═CR—)_(n)(CR═CR²—)_(m)R¹, and R⁵ is selected from the groupconsisting of —NR³R⁴, —R³, —OR³ and halo; and further wherein m is 0 or1, n is an integer from 0 to 10, R¹ and R² are independently selectedfrom the group consisting of —H, —CN, —COOR, CONHR, CON(H)OR, —SO₃R,—SO₂R —OSO₃R, —PO₃HR, and —OPO₃HR, further wherein at least one of R¹and R² is not —H, and if n=m=0 then R¹ is not —H; each R isindependently selected from —H and C₁₋₆ linear or branched alkyl; and R³and R⁴ are independently selected from the group consisting of H,substituted or unsubstituted linear or branched C₁-C₁₀ alkyl,substituted or unsubstituted phenyl, substituted or unsubstituted C₆-C₁₀aryl, substituted or unsubstituted C₅-C₁₀ heteroaryl, substituted orunsubstituted C₅-C₁₀ cycloalkyl, and substituted or unsubstituted C₅-C₁₀heterocycloalkyl; or R³ and R⁴ attached to their N together form a ringthat is substituted or unsubstituted C₅-C₁₀ heterocycloalkyl.

Further described herein are DSSCs incorporating a solar cell dye asdescribed above. Still further described herein are methods of makingDSSCs comprising the step of incorporating a solar cell dye as describedabove.

DETAILED DESCRIPTION Definitions

Unless specifically noted otherwise herein, the definitions of the termsused are standard definitions used in the art of organic chemistry andpharmaceutical sciences. Exemplary embodiments, aspects and variationsare illustrated in the figures and drawings, and it is intended that theembodiments, aspects and variations, and the figures and drawingsdisclosed herein are to be considered illustrative and not limiting.

While particular embodiments are shown and described herein, it will beobvious to those skilled in the art that such embodiments are providedby way of example only. Numerous variations, changes, and substitutionswill now occur to those skilled in the art. It should be understood thatvarious alternatives to the embodiments described herein may be employedin practicing the methods described herein. It is intended that theappended claims define the scope of the invention and that methods andstructures within the scope of these claims and their equivalents becovered thereby.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of skill in theart. All patents and publications referred to herein are incorporated byreference.

As used in the specification and claims, the singular form “a,” “an,”and “the” include plural references unless the context clearly dictatesotherwise.

Unless otherwise stated, structures depicted herein are also meant toinclude dyes which differ only in the presence of one or moreisotopically enriched atoms. For example, dyes as described hereinwherein one or more hydrogens are replaced by deuterium or tritium, orthe replacement of one or more carbon atoms by the ¹³C- or ¹⁴C-enrichedcarbon isotope. Further, substitution with heavier isotopes,particularly deuterium (²H or D) may afford certain therapeuticadvantages resulting from greater metabolic stability, increased in vivohalf-life, reduced dosage requirements or an improvement in therapeuticindex. It is understood that deuterium in this context is regarded as asubstituent of a dye of the formula (I).

The dyes described herein may also contain unnatural proportions ofatomic isotopes at one or more of atoms that constitute such dyes. Forexample, the dyes may be radiolabeled with radioactive isotopes, such asfor example tritium (³H), iodine-125 (¹²⁵I) or carbon-14 (¹⁴C). Allisotopic variations of the dyes described herein, whether radioactive ornot, are encompassed.

“Isomers” are different compounds that have the same molecular formula.“Stereoisomers” are isomers that differ only in the way the atoms arearranged in space. “Enantiomers” are a pair of stereoisomers that arenon-superimposable mirror images of each other. A 1:1 mixture of a pairof enantiomers is a “racemic” mixture. The term “(..+−..)” is used todesignate a racemic mixture where appropriate. “Diastereoisomers” arestereoisomers that have at least two asymmetric atoms, but which are notmirror-images of each other. The absolute stereochemistry is specifiedaccording to the Cahn-Ingold-Prelog R—S system. When a compound is apure enantiomer the stereochemistry at each chiral carbon can bespecified by either R or S. Resolved compounds whose absoluteconfiguration is unknown can be designated (+) or (−) depending on thedirection (dextro- or levorotatory) which they rotate plane polarizedlight at the wavelength of the sodium D line. Certain of the dyesdescribed herein contain one or more asymmetric centers and can thusgive rise to enantiomers, diastereomers, and other stereoisomeric formsthat can be defined, in terms of absolute stereochemistry, as (R)- or(S)-. The present chemical entities, pharmaceutical compositions andmethods are meant to include all such possible isomers, includingracemic mixtures, optically pure forms and intermediate mixtures.Optically active (R)- and (S)-isomers can be prepared using chiralsynthons or chiral reagents, or resolved using conventional techniques.The optical activity of a compound can be analyzed via any suitablemethod, including but not limited to chiral chromatography andpolarimetry, and the degree of predominance of one stereoisomer over theother isomer can be determined.

When the dyes described herein contain olefinic double bonds or othercenters of geometric asymmetry, and unless specified otherwise, it isintended that the dyes include both E and Z geometric isomers.

A “substituted” or “optionally substituted” group, means that a group(such as alkyl, aryl, heterocyclyl, cycloalkyl, hetrocyclylalkyl,arylalkyl, heteroaryl, or heteroarylalkyl) unless specifically notedotherwise, may have 1, 2 or 3 —H groups substituted by 1, 2 or 3substituents selected from halo, trifluoromethyl, trifluoromethoxy,methoxy, —COOH, —CHO, —NH₂, —NO₂, —OH, —SH, —SMe, —NHCH₃, —N(CH₃)₂, —CNand the like.

“Tautomers” are structurally distinct isomers that interconvert bytautomerization. “Tautomerization” is a form of isomerization andincludes prototropic or proton-shift tautomerization, which isconsidered a subset of acid-base chemistry. “Prototropictautomerization” or “proton-shift tautomerization” involves themigration of a proton accompanied by changes in bond order, often theinterchange of a single bond with an adjacent double bond. Wheretautomerization is possible (e.g. in solution), a chemical equilibriumof tautomers can be reached. An example of tautomerization is keto-enoltautomerization. A specific example of keto-enol tautomerization is theinterconversion of pentane-2,4-dione and 4-hydroxypent-3-en-2-onetautomers. Another example of tautomerization is phenol-ketotautomerization. A specific example of phenol-keto tautomerization isthe interconversion of pyridin-4-ol and pyridin-4(1H)-one tautomers.

Dyes described herein also include crystalline and amorphous forms ofthose dyes, including, for example, polymorphs, pseudopolymorphs,solvates, hydrates, unsolvated polymorphs (including anhydrates),conformational polymorphs, and amorphous forms of the dyes, as well asmixtures thereof. “Crystalline form,” “polymorph,” and “novel form” maybe used interchangeably herein, and are meant to include all crystallineand amorphous forms of the dye listed above, as well as mixturesthereof, unless a particular crystalline or amorphous form is referredto.

“Solvent,” “organic solvent,” and “inert solvent” each means a solventinert under the conditions of the reaction being described inconjunction therewith including, for example, benzene, toluene,acetonitrile, tetrahydrofuran (“THF”), dimethylformamide (“DMF”),chloroform, methylene chloride (or dichloromethane), diethyl ether,methanol, N-methylpyrrolidone (“NMP”), pyridine and the like. Unlessspecified to the contrary, the solvents used in the reactions describedherein are inert organic solvents. Unless specified to the contrary, foreach gram of the limiting reagent, one cc (or mL) of solvent constitutesa volume equivalent.

Compositions Dye-Sensitized Solar Cells

Dye-sensitized solar cells described herein comprise a photoanode, aphotocathode, and a redox electrolyte disposed between the photoanodeand the photocathode.

The photoanode comprises a metal oxide such as titanium dioxide. Theoxide can be in the form of nanoparticles such as mesoporous titaniumoxide nanoparticles. The photoanode is sensitized with a solar cell dyedeposited on a flexible metal, a transparent conducting substrate, or afluorine-doped tin oxide coated glass. The photocathode comprises acatalytic layer comprising one or more thin layers of platinum,polythiophenes including PEDOT, polyanilines, polypyrroles, or carbon(including carbon nanotubes and graphenes). The redox electrolyte iscommonly selected from a pair consisting of iodide/triiodide,Co(II)/Co(II) organic ligand complexes, and Cu(I)/Cu(II) organic ligandcomplexes.

Also described herein are solar cell dyes for use in a DSSC, wherein thedye is a compound of formula I:

wherein R⁶ is selected from the group consisting of —NR³R⁴, —R³, —OR³and halo;R⁵ is —(CR═CR—)_(n)(CR═CR²—)R¹;n is an integer from 0 to 10;R¹ and R² are independently selected from the group consisting of —H,—CN, —COOR, CONHR, CON(H)OR, —SO₃R, —SO₂R —OSO₃R, —PO₃HR, and —OPO₃HR,further wherein at least one of R¹ and R² is not —H;each R is independently selected from —H and C₁₋₆ linear or branchedalkyl; andR³ and R⁴ are independently selected from the group consisting of H,substituted or unsubstituted linear or branched C₁-C₁₀ alkyl,substituted or unsubstituted phenyl, substituted or unsubstituted C₆-C₁₀aryl, substituted or unsubstituted C₅-C₁₀ heteroaryl, substituted orunsubstituted C₅-C₁₀ cycloalkyl, and substituted or unsubstituted C₅-C₁₀heterocycloalkyl; or N, R³ and R⁴ together form a ring that issubstituted or unsubstituted C₅-C₁₀ heterocycloalkyl.

In some embodiments, the solar cell dye may be of formula II, III or IV:

where R⁵ and R⁶ are as described in the preceding paragraph.

The structures of the solar cell dyes described above, as shown informulae I-IV, have a central stilbene structure with two substituentmoieties, R5 and R6, attached thereto. One substituent moiety isattached to any position on each of the phenyl moieties, as shown informula I. For example, the substituent moieties may be attached topositions on the phenyl moieties as shown in formulae II-IV.

In general, the substituent moiety R⁶ will be a pi electron-donatingmoiety, and the other substituent moiety R⁵ will be a pielectron-withdrawing moiety. The pi electron-donating moiety may be anamino, alkyl or alkoxy moiety represented herein by —NR³R⁴, —R³, or—OR³. One alternative pi electron-donating moiety is the amino moiety—NR³R⁴, which may, for example, be selected from the group consisting ofdiethylamino, diphenylamino, methyl(phenyl)amino,cyclohexyl(methyl)amino, bis(4-methoxyphenyl)amino,bis(4-(tert-butyl)phenyl)amino, di(pyridin-2-yl)amino,di(pyridin-3-yl)amino, di(pyridin-4-yl)amino, piperidin-1-yl,4-methylpiperazin-1-yl, 4-phenylpiperazin-1-yl, pyrrolidin-1-yl, andmorpholino. In other embodiments, the pi electron-donating moiety is—R³, or —OR³, and may, for example, be selected from the groupconsisting of 3′,4′-dimethoxyphenyl, tert-butyl, phenyloxy, and methoxy.In still another alternative embodiment, the pi electron-donating moietyis halo selected from fluoro, bromo, chloro, and iodo. In oneembodiment, the halo is bromo.

The pi electron-withdrawing moiety R⁵ may be —H, —CN, —COOR, CONHR,CON(H)OR, —SO₃R, —SO₂R —OSO₃R, —PO₃HR, or —OPO₃HR, and maybe directlyattached to the central structure, or linked via from one to about tenconjugated carbon-carbon double bonds. This moiety is represented hereinby the structure —(CR═CR—)n(CR═CR²—)R¹, wherein n is an integer from 0to 10; and R¹ and R² are independently selected from the groupconsisting of —H, —CN, —COOR, CONHR, CON(H)OR, —SO₃R, —SO₂R —OSO₃R,—PO₃HR, or —OPO₃HR, further wherein at least one of R¹ and R² is not —H.As used herein, each R is independently selected from —H and C₁₋₆ linearor branched alkyl. In one alternative embodiment, R¹ and R² together are—CN and —COOH, n=0 and m=1.

In the solar cell dyes described herein, R³ and R⁴ are independentlyselected from the group consisting of H, substituted or unsubstitutedlinear or branched C₁-C₁₀ alkyl, substituted or unsubstituted phenyl,substituted or unsubstituted C₆-C₁₀ aryl, substituted or unsubstitutedC₅-C₁₀ heteroaryl, substituted or unsubstituted C₅-C₁₀ cycloalkyl, andsubstituted or unsubstituted C₅-C₁₀ heterocycloalkyl; or N, R³ and R⁴together form a ring that is substituted or unsubstituted C₅-C₁₀heterocycloalkyl. In alternative embodiments, R³ and R⁴ are methyl,ethyl, cyclohexyl, phenyl, 4-methoxyphenyl, 4-(tert-butyl)phenyl,pyridin-2-yl, pyridin-3-yl, or pyridin-4-yl, or N, R³ and R⁴ togetherare piperidin-1-yl, 4-methylpiperazin-1-yl, 4-phenylpiperazin-1-yl,pyrrolidin-1-yl, or morpholino.

The following exemplary solar cell dyes have been synthesized:

Entry Structure Compound # 1

WBI-PC-63 2

WBI-PC-64 3

WBI-PC-66 4

WBI-PC-81 5

WBI-PC-174 6

WBI-PC-78 7

WBI-PC-190 8

WBI-PC-191 9

WBI-PC-192

Also described herein are solar cell dyes for use in a DSSC, wherein thedye is a compound of formula V:

wherein either R⁶ is selected from the group consisting of —NR³R⁴, —R³,—OR³ and halo, and R⁵ is —(CR═CR—)n(CR═CR²—)_(m)R¹; orR⁶ is —(CR═CR—)_(n)(CR═CR²—)_(m)R¹, and R⁵ is selected from the groupconsisting of —NR³R⁴, —R³, —OR³ and halo; and further whereinm is 0 or 1;n is an integer from 0 to 10;R¹ and R² are independently selected from the group consisting of —H,—CN, —COOR, CONHR, CON(H)OR, —SO₃R, —SO₂R —OSO₃R, —PO₃HR, and —OPO₃HR,further wherein at least one of R¹ and R² is not —H, and if n=m=0 thenR¹ is not —H;each R is independently selected from —H and C₁₋₆ linear or branchedalkyl; andR³ and R⁴ are independently selected from the group consisting of H,substituted or unsubstituted linear or branched C₁-C₁₀ alkyl,substituted or unsubstituted phenyl, substituted or unsubstituted C₆-C₁₀aryl, substituted or unsubstituted C₅-C₁₀ heteroaryl, substituted orunsubstituted C₅-C₁₀ cycloalkyl, and substituted or unsubstituted C₅-C₁₀heterocycloalkyl; or N, R³ and R⁴ together form a ring that issubstituted or unsubstituted C₅-C₁₀ heterocycloalkyl.

For example, the solar cell dye may be of formula VI, VII or VIII:

The structures of the solar cell dyes described above, as shown informulae V-VII, have a phenyl-benzofuranyl central structure with twosubstituent moieties, R⁵ and R⁶, attached thereto. One substituentmoiety is attached to any position on the phenyl moiety, and the othersubstituent moiety is attached to any position on the phenyl ring of thebenzofuranyl moiety, as shown in formula I. For example, the substituentmoieties may be attached to positions on the phenyl and benzofuranylmoieties as shown in formulae VI-VIII.

In general, one of the substituent moieties (R⁵ or R⁶) will be a pielectron-donating moiety, and the other substituent moiety (R⁶ or R⁵)will be a pi electron-withdrawing moiety. The pi electron-donatingmoiety may be an amino, alkyl or alkoxy moiety represented herein by—NR³R⁴, —R³, or —OR³. One alternative pi electron donating moiety is theamino moiety —NR³R⁴, which may, for example, be selected from the groupconsisting of diethylamino, diphenylamino, methyl(phenyl)amino,cyclohexyl(methyl)amino, bis(4-methoxyphenyl)amino,bis(4-(tert-butyl)phenyl)amino, di(pyridin-2-yl)amino,di(pyridin-3-yl)amino, di(pyridin-4-yl)amino, piperidin-1-yl,4-methylpiperazin-1-yl, 4-phenylpiperazin-1-yl, pyrrolidin-1-yl, andmorpholino. In other embodiments, the pi electron-donating moiety is—R³, or —OR³, and may be selected from the group consisting of3′,4′-dimethoxyphenyl, tert-butyl, phenyoxy, and methoxy. In still otherembodiments, the pi electron-donating moiety is halo selected fromfluoro, bromo, chloro, and iodo. In one embodiment, the halo is bromo.

The pi electron-withdrawing moiety may be —H, —CN, —COOR, CONHR,CON(H)OR, —SO₃R, —SO₂R —OSO₃R, —PO₃HR, or —OPO₃HR, and maybe directlyattached to the central structure, or linked via from one to about tenconjugated carbon-carbon double bonds. This moiety is thereforerepresented herein by the structure —(CR═CR—)_(n)(CR═CR²—)_(m)R¹,wherein m is 0 or 1; n is an integer from 0 to 10; and R¹ and R² areindependently selected from the group consisting of —H, —CN, —COOR,CONHR, CON(H)OR, —SO₃R, —SO₂R —OSO₃R, —PO₃HR, or —OPO₃HR, furtherwherein at least one of R¹ and R² is not —H, and if n=m=0 then R¹ is not—H. As used herein, each R is independently selected from —H and C₁₋₆linear or branched alkyl. In one embodiment, R¹ and R² together are —CNand —COOH, n=0 and m=1.

In the solar cell dyes described herein, R³ and R⁴ are independentlyselected from the group consisting of H, substituted or unsubstitutedlinear or branched C₁-C₁₀ alkyl, substituted or unsubstituted phenyl,substituted or unsubstituted C₆-C₁₀ aryl, substituted or unsubstitutedC₅-C₁₀ heteroaryl, substituted or unsubstituted C₅-C₁₀ cycloalkyl, andsubstituted or unsubstituted C₅-C₁₀ heterocycloalkyl; or N, R³ and R⁴together form a ring that is substituted or unsubstituted C₅-C₁₀heterocycloalkyl. In alternative embodiments, R³ and R⁴ are methyl,ethyl, cyclohexyl, phenyl, 4-methoxyphenyl, 4-(tert-butyl)phenyl,pyridin-2-yl, pyridin-3-yl, or pyridin-4-yl, or N, R³ and R⁴ togetherare piperidin-1-yl, 4-methylpiperazin-1-yl, 4-phenylpiperazin-1-yl,pyrrolidin-1-yl, or morpholino.

Further exemplary solar cell dyes according to the present invention areshown in the Table below.

Compound Structure MW BC-146

380.40 BC-147

456.50 BC-149

456.50 BC-151

456.50 BC-152

455.52 BC-153

431.49 BC-154

437.50 BC-155

473.53 BC-156

516.55 BC-157

472.54 BC-158

568.72 BC-159

458.14 BC-160

503.55 BC-161

470.53 BC-162

368.19 BC-163

546.63 BC-165

425.44 BC-166

372.42 BC-167

345.40 BC-168

319.32 BC-169

374.40 BC-170

445.52 BC-171

381.39 BC-172

387.44 BC-173

360.41 BC-175

394.43 BC-176

405.45

Isolation and purification of the chemical entities and intermediatesdescribed herein can be effected, if desired, by any suitable separationor purification procedure such as, for example, filtration, extraction,crystallization, column chromatography, thin-layer chromatography orthick-layer chromatography, or a combination of these procedures.Specific illustrations of suitable separation and isolation procedurescan be had by reference to the examples herein. However, otherequivalent separation or isolation procedures can also be used.

When desired, the (R)- and (S)-isomers of the solar cell dyes describedherein, if present, may be resolved by methods known to those skilled inthe art, for example by formation of diastereomeric salts or complexeswhich may be separated, for example, by crystallization; via formationof diastereomeric derivatives which may be separated, for example, bycrystallization, gas-liquid or liquid chromatography; selective reactionof one enantiomer with an enantiomer-specific reagent, for exampleenzymatic oxidation or reduction, followed by separation of the modifiedand unmodified enantiomers; or gas-liquid or liquid chromatography in achiral environment, for example on a chiral support, such as silica witha bound chiral ligand or in the presence of a chiral solvent.Alternatively, a specific enantiomer may be synthesized by asymmetricsynthesis using optically active reagents, substrates, catalysts orsolvents, or by converting one enantiomer to the other by asymmetrictransformation.

The solar cell dyes described herein can be optionally contacted with apharmaceutically acceptable acid to form the corresponding acid additionsalts. Pharmaceutically acceptable forms of the solar cell dyes recitedherein include pharmaceutically acceptable salts, chelates, non-covalentcomplexes or derivatives, prodrugs, and mixtures thereof. In certainembodiments, the dyes described herein are in the form ofpharmaceutically acceptable salts. In addition, if the dye describedherein is obtained as an acid addition salt, the free base can beobtained by basifying a solution of the acid salt. Conversely, if theproduct is a free base, an addition salt, particularly apharmaceutically acceptable addition salt, may be produced by dissolvingthe free base in a suitable organic solvent and treating the solutionwith an acid, in accordance with conventional procedures for preparingacid addition salts from base compounds. Those skilled in the art willrecognize various synthetic methodologies that may be used to preparenon-toxic pharmaceutically acceptable addition salts.

When ranges are used herein for physical properties, such as molecularweight, or chemical properties, such as chemical formulae, allcombinations and subcombinations of ranges and specific embodimentstherein are intended to be included. The term “about” when referring toa number or a numerical range means that the number or numerical rangereferred to is an approximation within experimental variability (orwithin statistical experimental error), and thus the number or numericalrange may vary from, for example, between 1% and 15% of the statednumber or numerical range. The term “comprising” (and related terms suchas “comprise” or “comprises” or “having” or “including”) include thoseembodiments, for example, an embodiment of any composition of matter,composition, method, or process, or the like, that “consist of” or“consist essentially of” the described features.

EXPERIMENTAL

All reagents were purchased from commercial suppliers and used assupplied unless stated otherwise. Reactions were carried out in airunless stated otherwise. 400 MHz ¹H NMR spectra were obtained on a JEOLAS 400 spectrometer. Low-resolution mass spectra (LRMS) were obtained ona JEOL JMS-T100LC DART/AccuTOF mass spectrometer. Measurement ofreversal of protein aggregation may be carried out using such assays asBis-ANS Fluorescence as described in, for example, W. T. Chen et al., J.Biol. Chem, 2011, 286 (11), 9646.

General synthetic scheme for making the compounds in Examples 1-9herein:

Example 1 Synthesis of(Z)-3-[4-[(E)-2-[4-(4-tert-butyl-N-(4-tert-butylphenyl)anilino)phenyl]vinyl]-2,5-dimethoxy-phenyl]-2-cyano-prop-2-enoicacid (WBI-PC-63)

This is the synthetic scheme for Example 1.

Synthesis of Olefin Intermediate A

To a mixture of Bis((4-t-butyl)phenyl)amine (15.0 g, 0.053 mol) and4-bromostyrene (˜7 mL, 0.053 mol, 1 equiv.) in an oven dried 500 mLSchlenck flask was added Pd₂(dba)₃ (488 mg, 0.533 mmol), phosphine (360mg, 1.06 mmol) and NaOtBu (5.63 g, 0.059 mol). The flask was flushedwith N₂ for 10 min, treated with degassed 1,4-dioxane (50 mL) and themixture was heated to 80° C. for 1.5 hours under N₂. The reaction wasmonitored by TLC for completion before cooling to room temperature. Theorganic layer was washed with DI water (2×100 mL) and then saturatedbrine solution (100 mL). The combined organic layer was then dried withanhydrous Na₂SO₄ and concentrated. The resulting crude olefin was useddirectly in the following step without further purification.

Synthesis of Aldehyde Intermediate B

To the dark brown olefin (olefin intermediate A) in the Schlenck flaskunder N₂ was added 4-bromo-2,5-dimethoxy benzaldehyde (13.0 g, 0.053mol), N-methyl-dicylohexyl amine (23 mL, 0.112 mol), Pd₂(dba)₃ (488 mg,0.533 mmol), and the phosphine salt (307 mg, 1.06 mmol) under N₂. Dryand degassed 1,4-dioxane (25 mL) was then added to the flask and themixture was stirred at 60° C. under N₂ for 2.5 hours. The mixture turnedfrom purple to yellow green during the course of the reaction. CrudeLCMS showed the reaction was complete, and the mixture was filtered andthe collected solid washed with copious amounts of CH₂Cl₂ to separatethe product from the inorganic materials. The combined CH₂Cl₂/dioxanelayer was concentrated under reduced pressure. The resulting orange-redresidue was dissolved in CH₂Cl₂ (60 mL) and washed with 1N HCl (150 mL).The aqueous layer was extracted with CH₂Cl₂ (2×25 mL), and the combinedorganic layer was concentrated under reduced pressure to give a reddishyellow residue, which was dried on the vacuum line for 1 hour at roomtemperature and the resulting reddish yellow crude solid product wasused directly in the following reaction without further purification.

Synthesis of WBI-PC-63

To the aldehyde intermediate B was added glacial acetic acid (150 mL)followed by cyanoacetic acid (11.0 g, 0.129 mol) and ammonium acetate(12.3 g, 0.160 mol), and the reaction was refluxed for 5 hours. Thereaction was then cooled to room temperature, and was then slowly addedto ice-cold DI water (1.5 L), and stirred at room temperature for 1hour. The precipitate was filtered and washed with DI water and hexanes,and dried overnight in a vacuum oven at 60° C. to afford WBI-PC-63 as adark red solid. (31.5 g; 95% overall yield). LCMS (M+1): 615.3; 1H NMR(400 MHz, d6-DMSO): 8.52 (s, 1H), 7.85 (s, 1H), 7.46-6.86 (m, 15H), 3.94(s, 3H), 3.83 (s, 3H), 1.26 (s, 18H).

Example 2 Synthesis of(Z)-2-cyano-3-[4-[(E)-2-[4-(N-phenylanilino)phenyl]vinyl]phenyl]prop-2-enoicacid (WBI-PC-64) Synthetic Scheme

Synthesis of Olefin Intermediate A

The starting aldehyde (4.5 g, 0.0165 mol) was placed in a pear shapedflask with 25 mL of dry THF and the yellow solution was degassed for 20min with N₂. KOtBu (2.5 g, 1.25 equiv.) and methyltriphenylphosphoniumiodide (8.33 g, 1.25 equiv.) were combined in a separate 250 mL Schlenckflask equipped with a stir bar and placed under N₂. The THF solution ofA was then cannula transferred under N₂ into the Schlenck flask. Thesolution was stirred at room temperature under N₂ for 5 hr. The reactionmixture was partitioned between 125 mL of CH₂Cl₂ and 100 mL of DI water.The mixture was acidified using concentrated HCl (pH˜4). The separatedorganic layer was then washed with DI water (2×100 mL) and thensaturated brine solution (100 mL). The combined organic layer was thendried over anhydrous Na₂SO₄ and concentrated under reduced pressure. 1HNMR of the crude product confirmed the formation of the desired Wittigproduct. The crude material was then purified on silica gel usingn-hexanes as the eluent to afford 3.10 g of olefin product A as a whitesolid (78% yield).

Synthesis of Aldehyde Intermediate B

A Schlenck flask was charged sequentially with A (1.00 g, 3.69 mmol),4-bromobenzaldehyde (310 mg, 1.68 mmol), Pd₂(dba)₃ (15 mg), sodiumcarbonate (444 mg, 1.13 equiv.), and 2,6-di-t-butylcresol (732 mg, 0.33mmol). The reaction mixture was then treated with dry dimethylacetamide(DMAC, 10 mL) and the flask flushed with N₂ for 20 min at roomtemperature. The reaction was then placed in an oil bath at 120° C.under N₂ for 24 hours. The color of the solution changed from lightyellow to dark yellow. The reaction was stopped and CH₂Cl₂ (100 mL) wasadded, and washed with of DI water (2×100 mL). The organic layer waswashed with saturated brine solution (100 mL), dried over anhydrousNa₂SO₄, and concentrated under reduced pressure. The crude product wasthen purified on silica gel using hexanes/CH₂Cl₂ (85:15) as the eluentto give the desired aldehyde product B as a yellow solid (600 mg, 45%yield).

Synthesis of WBI-PC-64

Combined B (404 mg, 1.076 mmol) was treated with cyanoacetic acid (92mg, 1 equiv.) and piperidine (0.22 mL, 2 equiv.) in 30 mL of dry MeCNand flushed with N₂ at room temperature for 15 min. The reaction flaskwas then placed into an oil bath (82° C.) and refluxed under N₂ for 18hours. The reaction turned from yellow to orange red and becamehomogeneous. The reaction was stopped, allowed to cool to roomtemperature and the solvent removed under reduced pressure. The residuewas placed in a separatory funnel with 100 mL of CH₂Cl₂. The organiclayer was washed with 0.1 N HCl solution (100 mL) and DI water (100 mL).The organic layer was then dried over anhydrous Na₂SO₄ and dried underreduced pressure to yield WBI-PC-64 (350 mg, 79% yield) as dark redcrude product. LCMS (M+1): 443.1; 1H NMR (400 MHz, d6-DMSO): 8.29 (s,1H), 8.10 (s, 2H), 7.75 (s, 2H), 7.32-6.92 (m, 16H).

Example 3 Synthesis of(E)-2-cyano-3-[4-[(E)-2-[4-(3,6-ditert-butylcarbazol-9-yl)phenyl]vinyl]-2,5-dimethoxy-phenyl]prop-2-enoicacid (WBI-PC-66) Synthetic Scheme

Synthesis of Olefin Intermediate A

Bis(3,6-t-butyl)carbazole (0.0053 mol) and 4-bromostyrene (˜0.7 mL,10.0053 mol, equiv.) were combined in an oven dried 100 mL Schlenckflask with Pd₂(dba)₃ (48 mg, 0.0533 mmol), phosphine (36 mg, 1.06 mmol)and NaOtBu (0.56 g, 0.0059 mol). The flask was flushed with N₂ for 10min, then dry, degassed 1,4-dioxane (10 mL) was added and the reactionwas heated at 80° C. for 1.5 hours under N₂. The reaction was monitoredby TLC to confirm consumption of starting materials and then cooled toroom temperature. The organic layer was washed with DI water (2×25 mL),then saturated brine solution (25 mL). The organic layer was dried overanhydrous Na₂SO₄ and concentrated under reduced pressure. The resultingcrude olefin intermediate A was used in the following step withoutfurther purification.

Synthesis of Aldehyde Intermediate B

The olefin intermediate A (5.0 mmol) was mixed with 4-bromo benzaldehyde(1.39 g, 5.0 mmol, 1.5 equiv.) in a 100 mL Schlenck vessel with drytoluene (30 mL) and flushed with N₂ for 20 min. To this solution wereadded Pd(dba)3 (92 mg, 2 mol %), tricyclohexylphosphine (57 mg, 4 mol %)and NaOtBu (724 mg, 1.5 equiv.) under N₂. The reaction mixture was thenrefluxed for 18 hours under N₂. The reaction was stopped and allowed tocool to room temperature. The mixture was treated with DI water (25 mL),the organic layer was then washed sequentially with 1 N HCl (25 mL) andsaturated brine (25 mL) solution. The organic layer was concentratedunder reduced pressure and purified on silica gel column usingHexanes:DCM to give the aldehyde product B as a yellow solid (2.54 g,78% yield).

Synthesis of WBI-PC-66

The aldehyde intermediate B (0.82 g, 2.70 mmol, oily solid) was placedin a RB flask with cyanoacetic acid (505 mg, 2.2 equiv.). Piperidine(1.23 mL, 4.6 equiv.) was added with 15 mL of dry MeCN. The mixture wasplaced under N₂ and stirred for 15 min. The mixture was then refluxedfor 12 hours under N₂. The reaction was stopped and the MeCN wasconcentrated under reduced pressure to yield a residue. The residue wasdissolved in 100 mL of EtOAC and washed with 50 mL of DI water. Theorganic layer was then washed with 0.1N HCl (75 mL). The organic layerwas then analyzed by TLC and DART/MS (negative ion mode) and productformation was confirmed. The organic layer was concentrated underreduced pressure and the crude product was purified on silica gel usingDCM:MeOH (100:0 to 90:10) to afford WBI-PC-66 as a yellowish red solid.1H NMR (400 MHz, d6-DMSO) δ 8.54 (s, 1H), 8.29 (d, 2H), 7.89− (m, 10H),5.75 (s, 2H), 3.98, 3.88 (2s, 3H), 1.41 (s, 18H).

Example 4 Synthesis of(Z)-2-cyano-3-[5-[4-(N-phenylanilino)phenyl]-2-furyl]prop-2-enoic acid(WBI-PC-81) Synthetic Scheme

Synthesis of Aldehyde Intermediate A

A mixture of 4-bromo-N,N-diphenyl-aniline (1.0 g, 3.08 mmol),PdCl2(dppf) (250 mg, 10 mol %), K2CO3 (2.12 g, 5 equiv.) were combinedwith 15 mL of dry toluene in a Schlenck tube and stirred under N₂ for 15min at room temperature. The mixture was treated with (5-formyl-2-furyl)boronic acid (964 mg, 2 equiv.) in dry MeOH (5 mL), and the reaction wasrefluxed for 18 hours under N₂. The mixture was then cooled to roomtemperature and the solvents were removed under reduced pressure. Theresulting residue was treated with DI water (20 mL) and extracted withDCM (50 mL). The organic layer was sequentially washed with DI water (20mL), 1N HCl (25 mL) and saturated brine solution (25 mL). The organiclayer was concentrated under reduced pressure and purified on silica gelusing Hexanes: EtOAc as eluent to afford5-[4-(N-phenylanilino)phenyl]furan-2-carbaldehyde (A) as a yellow redsolid (900 mg, 82% yield).

Synthesis of WBI-PC-81

5-[4-(N-phenylanilino)phenyl]furan-2-carbaldehyde A (640 mg, 1.80 mmol)was combined with cyanoacetic acid (382 mg, 2.5 eq) and piperidine(0.931 mL, 2.1 eq with respect to cyanoacetic acid) in 10 mL of dryMeCN. The reaction was refluxed for 4 hours whereby the TLC indicatedconsumption of all starting material. The reaction was cooled down toroom temperature and the MeCN was removed under reduced pressure. To theresidue was added EtOAc (50 mL), washed with DI water (50 mL) followedby 0.1 N HCl (50 mL). The organic layer was separated, concentrated andthen the crude mixture was then purified using a silica gel column usingDCM: MEOH as eluent to afford WBI-PC-81 as a dark red solid (600 mg, 79%yield). LCMS (M+1): 407.1; 1HNMR (400 MHz, d6-DMSO) 7.99 (s, 1H), 7.77(s, 2H), 7.60 (s, 1H), 7.40 (m, 4H), 7.22-7.08 (m, 7H), 6.94 (s, 2H).

Example 5 Synthesis of7-[(E)-2-[4-(4-tert-butyl-N-(4-tert-butylphenyl)anilino)phenyl]vinyl]-2-oxo-1H-quinoline-3-carbonitrile(WBI-PC-174) Synthetic Scheme

Synthesis of Olefin Intermediate A

To a mixture of Bis((4-t-butyl)phenyl)amine (15.0 g, 0.053 mol) and4-bromostyrene (˜7 mL, 1 equiv.) in an oven dried 500 mL Schlenck flaskwas added Pd₂(dba)₃ (488 mg, 0.533 mmol), phosphine (360 mg, 1.06 mmol)and NaOtBu (5.63 g, 0.059 mol). The flask was flushed with N₂ for 10 minand treated with degassed 1,4-dioxane (50 mL) was added, and the mixturewas heated at 80° C. for 1.5 hours under N₂. The reaction was monitoredby TLC for completion before cooling to room temperature. The organiclayer was washed with DI water (2×100 mL) and then saturated brinesolution (100 mL). The organic layer was then dried over anhydrousNa₂SO₄ and concentrated under reduced pressure. The resulting crudeolefin product was used in the following step without furtherpurification.

Synthesis of WBI-PC-174

1.0 equiv. of 7-bromo-2-oxo-1H-quinoline-3-carbonitrile, 0.025 equiv.Pd₂(dba)₃ and 0.05 equiv. tBu3PHBF4 were added to 1.0 equiv. ofN,N-bis(4-tert-butylphenyl)-4-vinyl-aniline in a round bottom flask. Theflask was purged with N₂ for 20 min. Dry dioxane was degassed bybubbling with N₂ for 20 minutes. Dioxane was added to the reaction (0.2M) followed by 1.5 equiv. N-methyl-di-cyclohexylamine. The solution washeated to 65° C. and monitored by LCMS, TLC 30% ethyl acetate/hexane.After 1.5 hours, the reaction had solidified. 4.0 mL of N₂ degassed drydioxane were added to re-dissolve the material and the styrene wasconsumed within 2.5 hours as indicated by TLC. The reaction mixture, asolid mass, was cooled to room temperature, residual solvent was removedunder reduced pressure. The crude reaction product was partitionedbetween 50 mL of CH₂Cl₂ and 20 mL of 1M HCl and the insoluble materialwas filtered off. The layers were separated and the aqueous layer wasback extracted 2×25 mL of CH₂Cl₂. The combined organic layer was driedover Na₂SO₄, filtered and concentrated under reduced pressure to affordWBI-PC-174. 1HNMR (400 MHz, d6-DMSO) 8.10 (s, 1H), 7.60-6.91 (m, 17H),1.26 (s, 18H).

General Synthetic Scheme for Making Compounds with Acid Linkers

Example 6 Synthesis of(Z)-3-[2-(carboxymethoxy)-4-[(E)-2-[4-(N-phenylanilino)phenyl]vinyl]phenyl]-2-cyano-prop-2-enoicacid (WBI-PC-78) Synthetic Scheme

Synthesis of the Bromoaldehyde Intermediate with Acid Linker (A)

A mixture of 4-bromo-2-hydroxybenzaldehyde (1.5 g, 7.4 mmol), tert-butyl6-bromohexanoate (9.0 mmol) and potassium carbonate (3.2 g, 22.5 mmol)were taken in acetone (10 mL). The reaction mixture was refluxed for 4h. The reaction mixture was extracted with ethyl acetate (2×25 mL),dried over anhydrous Na₂SO₄ and concentrated under reduced pressure.Purification on silica gel afforded 1.1 g of the desired compound A as awhite solid.

Synthesis of the Aldehyde Intermediate with Acid Linker (B)

To the N,N-diphenyl-4-vinyl-aniline (0.003 mol) in a two necked flaskunder N₂ was added the bromo-aldehyde intermediate A (0.004 mol) andN-methyl-dicylohexyl amine (0.008 mol). Pd₂(dba)₃ (0.04 g, 0.044 mmol)and phosphine salt (0.022 g, 0.007 mmol) were then added to the flaskunder N₂. Dry and degassed 1,4-dioxane (10 mL) was added to the flask.The mixture was stirred at 70° C. under N₂ for 2.5 hours. The reactionmixture was extracted with ethyl acetate, dried over anhydrous Na₂SO₄and concentrated under reduced pressure. Purification on silica gelafforded 1.4 g of the desired compound B.

Synthesis of WBI-PC-78

In a 20 mL microwave tube, the intermediate B (3 mmol), 2-cyanoaceticacid (5.1 mmol) and ammonium acetate (8 mmol) were mixed in acetic acid(15 mL). The reaction mixture was heated at 130° C. for 90 min. Water(10 mL) was added, and the solid was filtered, and dried under reducedpressure to give the product WBI-PC-78. LCMS (M+1): 559.7; 1H NMR (400MHz, d6-DMSO) 8.54 (s, 1H), 8.17 (s, 1H), 7.32-7.30 (m, 9H), 7.06-7.03(m, 9H), 4.19 (t, 2H), 2.47 (t, 2H), 1.88-1.66 (m, 4H).

Example 7 Synthesis of(Z)-3-[2-(carboxymethoxy)-4-[(E)-2-[4-(N-phenylanilino)phenyl]vinyl]phenyl]-2-cyano-prop-2-enoicacid WBI-PC-190 Synthetic Scheme

Synthesis of the Bromoaldehyde Intermediate with Acid Linker

In a 250 mL round bottom flask, 4-bromo-2-hydroxybenzaldehyde (3 g, 14.9mmol), tert-Butyl bromoacetate (3.49 g, 17.9 mmol) and potassiumcarbonate (6.19 g, 44.8 mmol) were dissolved in acetone (30 mL). Thereaction mixture was refluxed for 4 hours. The reaction mixture was thenextracted with ethyl acetate (2×25 mL), dried over anhydrous Na₂SO₄ andconcentrated under reduced pressure. Purification on silica gel afforded2.8 g (59% yield) of the desired compound A as white solid. 1H NMR (400MHz, CDCl3): 10.46 (s, 1H), 7.71 (d, 1H), 7.24 (s, 1H), 6.99 (s, 1H),4.61 (s, 2H), 1.47 (s, 9H).

Synthesis of the Aldehyde Intermediate with Acid Linker

To the N,N-diphenyl-4-vinyl-aniline (2 g, 0.007 mol) in a two neckedflask under N₂ was added 4-bromo-2,5-dimethoxy benzaldehyde (2.44 g,0.008 mol) and N-methyl-di-cyclohexyl amine (3.3 mL, 0.016 mol).Pd₂(dba)₃ (0.081 g, 0.088 mmol) and phosphine salt (0.043 g, 0.0014mmol) were then added to the flask under N₂. Dry and degassed1,4-dioxane (10 mL) was added to the flask. The mixture was stirred at70° C. under N₂ for 2.5 hours. The mixture turned from purple to yellowgreen upon stirring. TLC analysis (Hex:Ethyl acetate 10:1) after 2.5hours showed complete consumption of 4-bromo-2,5-dimethoxy benzaldehydeand the formation of the desired product (confirmed by LCMS). Thereaction mixture was extracted with ethyl acetate, dried over anhydrousNa₂SO₄ and evaporated. Purification by combiflash afforded 2.2 g ofdesired compound B. LCMS (M+1): 505.9; 1H NMR (400 MHz, CDCl3): 10.48(s, 1H), 7.80 (d, 1H), 7.40-7.04 (m, 19H), 6.99 (s, 1H), 4.67 (s, 2H),1.47 (s, 9H).

Synthesis of WBI-PC-190

In a 20 mL microwave tube, tert-butyl2-[2-formyl-5-[(E)-2-[4-(N-phenylanilino)phenyl]vinyl]-phenoxy]-acetate(1.3 g, 3 mmol), 2-cyanoacetic acid (0.46 g, 5.1 mmol) and ammoniumacetate (0.595 g, 8 mmol) were mixed in 15 mL of acetic acid. Thereaction mixture was heated at 130° C. for 20 min. LCMS showed desiredmass peak along with tertiary group deprotected product. Water (10 mL)was added, and the solid was filtered, and dried under reduced pressureto give the product WBI-PC-190 (0.6 g, 83% yield) red solid. LCMS (M+1):516.6; 1H NMR (400 MHz, d6-DMSO): 8.60 (s, 1H), 8.18 (s, 1H), 7.34-6.98(m, 20H), 4.92 (s, 2H).

Example 8 Synthesis of WBI-PC-191 Synthesis oftert-Butyl-8-bromooctanoic acid Intermediate

To a solution of 8-bromooctanoic acid (5 g, 22 mmol) in DCM (20 mL) wasadded TFAA (10.36 g, 49 mmol) dropwise at 0° C. After 2.5 hours, t-BuOH(5.81 g, 70 mmol) was slowly added. After 1 hour, the reaction hadwarmed to rt. After 2.5 hours, the reaction was quenched with H2O (10mL) and extracted with ethyl acetate (2×20 mL). The combined organiclayer was washed with brine and dried over MgSO₄, filtered, andconcentrated under reduced pressure. The crude (6.89 g) was used in thenext step without further purification.

Synthesis of the aldehyde Intermediate by O-alkylation of4-bromo-2-hydroxy-benzaldehyde with tert-butyl ester Linker

In a single necked round bottom flask, 4-bromo-2-hydroxy-benzaldehyde (3g, 0.015 mol),tert-butyl 8-bromooctanoate (4.16 g, 0.015 mol) and K2CO3(4.12 g, 0.03 mol) were dissolved in dry DMF (30 mL). The reactionmixture was heated at 70° C. for 16 hours. LCMS showed the desired masspeak. The crude reaction mixture was extracted with ethyl acetate,washed with water, dried over anhydrous Na₂SO₄ and concentrated underreduced pressure. Purification on silica gel using Hexane/Ethyl acetate(97:3) afforded 2.4 g (40% yield) of desired product. 1H NMR (400 MHz,CDCl3): 10.39 (s, 1H), 7.67 (d, 1H), 7.11 (d, 2H), 4.03 (t, 2H), 2.21(t, 2H), 1.80-1.23 (m, 10H), 1.41 (s, 9H).

Synthesis of the triphenylamine styryl aldehyde Intermediate tert-butylester Linker Product

To the N,N-diphenyl-4-vinyl-aniline (2 g, 0.007 mol) in a two neckedflask under N₂ was added tert-butyl8-(5-bromo-2-formyl-phenoxy)octanoate (3.09 g, 0.008 mol) andN-methyl-dicylohexyl amine (3.05 g, 0.0.016 mol). Pd₂(dba)₃ (0.081 g,0.088 mmol) and phosphine salt (0.043 g, 0.0014 mmol) were then added tothe flask under N₂. Dry and degassed 1,4-dioxane (10 mL) was added tothe flask. The mixture was stirred at 70° C. under N₂ for 2.5 hours. Themixture turned from purple to yellow green upon stirring. TLC analysis(Hexane:Ethyl acetate 10:1) after 2.5 hours showed complete consumptionof tert-butyl 8-(5-bromo-2-formyl-phenoxy)octanoate and the formation ofthe desired product (confirmed by LCMS). Purification on silica gelafforded 2.3 g (50% yield) of the desired product. 1H NMR (400 MHz,CDCl3): 10.40 (s, 1H), 7.66 (d, 1H), 7.13 (d, 2H), 4.04 (t, 2H), 2.19(t, 2H), 1.81-1.28 (m, 14H), 1.41 (s, 9H).

Synthesis of the cyanoacrylic acid Intermediate by KnoevenagelCondensation

In a 20 mL microwave tube, tert-butyl8-[2-formyl-5-[(E)-2-[4-(N-phenylanilino)phenyl]vinyl]phenoxy]octanoate(1.5 g, 3 mmol), 2-cyanoacetic acid (0.454 g, 5 mmol) and ammoniumacetate (0.588 g, 8 mmol) were dissolved in 15 mL of acetic acid. Thereaction mixture was heated at 130° C. for 20 min. LCMS showed thedesired mass peak along with tertiary group deprotected product. Water(10 mL) was added and filtered. The collected solid was used in the nextstep without further purification.

Synthesis of WBI-PC-191 by tert-butyl Deprotection

In a 20 mL microwave tube,(Z)-3-[2-(8-tert-butoxy-8-oxo-octoxy)-4-[(E)-2-[4-(N-phenylanilino)phenyl]vinyl]phenyl]-2-cyano-prop-2-enoicacid (1 g, 1.52 mmol) was dissolved in 10 mL acetic acid and 1 mL water.The reaction mixture was heated at 130° C. for 20 min. The reaction wasrepeated two times for 20 min each in the microwave. LCMS showed thedesired mass peak. Water (10 mL) was added and filtered. The collectedsolid was dried under reduced pressure to give WBI-PC-191 0.650 g (61%ield) as a red solid. LCMS (M+1): 600.7; 1H NMR (400 MHz, d6-DMSO): 8.56(s, 1H), 8.18 (s, 1H), 7.60-6.91 (m, 20H), 4.16 (br s, 2H), 2.18 (br s,2H), 1.89 (br s, 2H), 1.58-1.20 (m, 8H).

Example 9 Synthesis of WBI-PC-192 Synthesis of thetert-Butyl-10-bromodecanoic acid Intermediate

To solution of 10-bromdectanoic acid (5 g, 20 mmol) in DCM (20 mL) wasadded TFAA (9.2 g, 44 mmol) dropwise at 0° C. After 2.5 hours, t-BuOH(5.16 g, 70 mmol) was slowly added. After 1 hour the reaction had warmedto RT. After 2.5 hours, the reaction was quenched with H₂O (5 mL) andextracted with ethyl acetate (2×20 mL). The combined organic layer waswashed with brine and dried over MgSO₄, filtered, and concentrated underreduced pressure. The crude (6.12 g) was used in the next step withoutfurther purification.

Synthesis of the aldehyde Intermediate by O-alkylation of4-bromo-2-hydroxy-benzaldehyde with tert-butyl ester Linker

In a single necked round bottom flask, 4-bromo-2-hydroxy-benzaldehyde (3g, 0.015 mol), tert-butyl 10-bromodecanoate (5.04 g, 0.016 mol) andK2CO3 (6.18 g, 0.045 mol) were dissolved in dry DMF (30 mL). Thereaction mixture was heated at 70° C. for 16 hours. LCMS showed thedesired mass peak. The crude reaction mixture was extracted with ethylacetate, washed with water, dried over anhydrous Na₂SO₄ and concentratedunder reduced pressure. Purification on silica gel afforded 3.2 g (50%yield) of the desired product.

Synthesis of the triphenylamine styryl aldehyde intermediate tert-butylester Linker

To the N,N-diphenyl-4-vinyl-aniline (2 g, 7.74 mmol) in a two neckedflask under N₂ was added tert-butyl10-(5-bromo-2-formyl-phenoxy)decanoate(3.307 g, 7.75 mmol) andN-methyl-dicyclohexyl amine (3.05 g, 15.56 mmol). Pd₂(dba)₃ (0.081 g,0.8 mmol) and tri-tert-butylphosphonium tetrafluoroborate (0.043 g, 1.4mmol) were then added to the flask under N₂. Dry and degassed1,4-dioxane (10 mL) was added to the flask. The mixture was stirred at70° C. under N₂ for 2.5 hours. The mixture turned from purple to yellowgreen upon stirring. TLC analysis (Hexane:Ethyl acetate 10:1) after 2.5hours showed complete consumption of tert-butyl10-(5-bromo-2-formyl-phenoxy)decanoate and the formation of the desiredproduct (confirmed by LCMS). Purification on silica gel afforded 2.3 gof desired product as a yellow liquid. 1H NMR (400 MHz, d6-DMSO): 10.43(s, 1H), 7.82 (s, 1H), 7.41-6.98 (m, 16H), 4.10 (t, 2H), 2.20 (t, 2H),1.90-1.209 (m, 14H), 1.42 (s, 9H).

Synthesis of the cyanoacrylic acid intermediate by KnoevenaqelCondensation

In a 20 mL microwave tube, tert-butyl10-[2-formyl-5-[(E)-2-[4-(N-phenylanilino)phenyl]vinyl]phenoxy]-decanoate(1.5 g, 2.43 mmol), 2-cyanoacetic acid (0.434 g, 5.1 mmol) and ammoniumacetate (0.561 g, 7.23 mmol) were dissolved in 15 mL acetic acid. Thereaction mixture was heated at 130° C. for 20 min. LCMS showed thedesired mass peak along with the tertiary group deprotected product.Water (10 mL) was added and filtered. The collected solid was used inthe next step without further purification.

Synthesis of WBI-PC-192 by tert-butyl Deprotection

In a 20 mL microwave tube,(Z)-3-[2-(10-tert-butoxy-10-oxo-decoxy)-4-[(E)-2-[4-(N-phenylanilino)-phenyl]vinyl]phenyl]-2-cyano-prop-2-enoicacid(0.9 g, 1.31 mmol) was dissolved in 20 mL of acetic acid. Thereaction mixture was heated at 130° C. for 20 min. The reaction wasrepeated two times for 20 min each in the microwave. LCMS showed thedesired mass peak. Water (10 mL) was added and filtered. The collectedsolid was dried under reduced pressure to give 0.650 g (61% yield) ofWBI-PC-192 as a red solid. LCMS (M+1): 628.7; 1H NMR (400 MHz, d6-DMSO):8.54 (s, 1H), 8.19 (s, 1H), 7.61-6.90 (m, 20H), 4.18 (br s, 2H), 2.20(br s, 2H), 1.88 (br s, 2H), 1.58-1.20 (m, 12H).

Example 10 Synthesis of BC-146 and -147

The two compounds BC-146[2-cyano-3-(6-(diphenylamino)benzofuran-2-yl)acrylic acid] and BC-147[2-cyano-3-(4-(6-(diphenylamino)benzofuran-2-yl)phenyl)acrylic acid]were synthesized from common intermediate 3-hydroxytriphenylamine. The3-hydroxy functional group on triphenylamine enables a cyclization thatincorporates one of the three phenyl groups as the benzo ring of thebenzofuran.

A. Synthesis of 3-Hydroxytriphenylamine

The synthesis of 3-hydroxytriphenylamine was adapted from a procedurereported by M.-k. Leung et al., Organic Letters (2006) 8:2623-2626. To anitrogen purged flask containing 3-methoxytriphenylamine (2.90 g) wasadded anhydrous dichloromethane (21 mL). The reaction was cooled to −78°C. and boron tribromide (1.0 M in dichloromethane, 21 mL) was addeddropwise over 10 minutes via syringe. The reaction was allowed to warmto room temperature slowly over 18 hours. The reaction was quenched bythe careful addition of a 10% aqueous solution of potassium carbonate.The reaction was then allowed to stir at room temperature for 20 minutesbefore being extracted with dichloromethane (2×50 mL). The combinedextract was washed with brine, dried over magnesium sulfate, filtered,and concentrated to afford 3-hydroxytriphenylamine (2.75 g) which wasused without further purification. ¹H NMR (400 MHz, Chloroform-d) δ7.27-7.21 (m, 4H), 7.11-7.05 (m, 5H), 7.04-6.98 (m, 2H), 6.63 (ddd, 1H),6.52 (t, 1H), 6.45 (ddd, Hz, 1H), 4.50 (broad s, 1H).

B. Synthesis of 4-(Diphenylamino)-2-hydroxybenzaldehyde

A solution of 3-hydroxytriphenylamine (1.47 g) in anhydrousN,N-dimethylformamide (28 mL) was cooled to 0° C. In a separate flask,phosphorous oxychloride (1.57 mL) was added dropwise toN,N-dimethylformamide (28 mL) at 0° C. After 10 minutes, the phosphorousoxychloride solution was added dropwise to the reaction via cannula over20 minutes. The reaction mixture was stirred at 0° C. for 3 hours thenquenched by the addition of water (20 mL) and warmed to roomtemperature. The aqueous mixture was extracted with dichloromethane(4×50 mL), and then the combined dichloromethane fractions washed withwater (50 mL) and brine (50 mL). The dichloromethane solution was driedover magnesium sulfate, filtered and concentrated. The residue waspurified via chromatography on silica gel (elution with 0 to 10% ethylacetate in hexanes) to afford 4-(diphenylamino)-2-hydroxybenzaldehyde(1.07 g). ¹H NMR (400 MHz, Chloroform-d) δ 11.40 (s, 1H), 9.59 (s, 1H),7.35 (dd, 4H), 7.22-7.15 (m, 7H), 6.46 (dd, 1H), 6.34 (d, 1H).

C. Synthesis of 2-(2,2-Diethoxyethoxy)-4-(diphenylamino)benzaldehyde

A flask containing 4-(diphenylamino)-2-hydroxybenzaldehyde (0.50 g) andpotassium carbonate (0.26 g) was flushed with nitrogen for 20 minutes.Anhydrous N,N-dimethylformamide (3.5 mL) and bromodiethoxyethane (0.33mL) were added and the reaction heated to 155° C. for 2 hours. Thereaction was cooled to room temperature and water added (15 mL). Theaqueous layer was extracted with ethyl acetate (3×30 mL) and thecombined organic fractions washed with water and brine, dried oversodium sulfate, filtered and concentrated to afford2-(2,2-diethoxyethoxy)-4-(diphenylamino)benzaldehyde (0.70 g) which wasused without further purification. ¹H NMR (400 MHz, Chloroform-d) δ10.26 (d, 1H), 7.65 (d, 1H), 7.38-7.27 (m, 4H), 7.21-7.10 (m, 6H), 6.53(ddd, 1H), 6.42 (d, 1H), 4.79 (t, 1H), 3.83 (d, 2H), 3.79-3.67 (m, 2H),3.59 (m, 2H), 1.21 (t, 6H).

D. Synthesis of 6-(diphenylamino)benzofuran-2-carbaldehyde

A solution of 2-(2,2-diethoxyethoxy)-4-(diphenylamino)benzaldehyde (0.21g) in acetic acid (2.5 mL) was heated to reflux. After 5.5 hours, thereaction was cooled to room temperature and diluted with ethyl acetate(30 mL). The organic layer was washed with saturated sodium bicarbonateuntil the washes remained basic (4×10 mL). The combined aqueous washeswere extracted with ethyl acetate (2×30 mL) and the combined organicfractions then washed with saturated sodium bicarbonate and brine. Theorganic layer was dried over magnesium sulfate, filtered andconcentrated. The residue was purified via chromatography on silica gel(elution with 20% ethyl acetate in hexanes) to afford6-(diphenylamino)benzofuran-2-carbaldehyde (0.12 g). ¹H NMR (400 MHz,Chloroform-d) δ 9.72 (s, 1H), 7.51 (d, 1H), 7.45 (d, 1H), 7.33-7.26 (m,4H), 7.17-7.07 (m, 7H), 7.05 (dd, 1H).

E. Synthesis of 2-Cyano-3-(6-(diphenylamino)benzofuran-2-yl)acrylic acid(BC-146)

To a solution of 6-(diphenylamino)benzofuran-2-carbaldehyde (0.16 g) inacetonitrile (2.6 mL) was added cyanoacetic acid (0.049 g) andpiperidine (0.078 mL). The reaction was heated to reflux for 2 hoursthen cooled to room temperature. Water (10 mL) was added and the pH ofthe reaction adjusted to 2-3 with 1M HCl. The combined aqueous layer wasextracted with dichloromethane (4×20 mL) and then the combined organicfractions dried over sodium sulfate, filtered and concentrated. Thesolid was dried under vacuum at 60° C. to afford2-cyano-3-(6-(diphenylamino)benzofuran-2-yl)acrylic acid (BC-146, 0.19g) as a single, unidentified olefin isomer. ¹H NMR (400 MHz, DMSO-d6) δ13.78 (s, 1H), 8.08 (s, 1H), 7.72 (s, 1H), 7.64 (d, 1H), 7.35 (t, 4H),7.13 (dd, 6H), 6.90 (dd, 1H), 6.84 (s, 1H). Mass (m/z): 381 (M+1)+.

F. Synthesis of 5-(Diphenylamino)-2-iodophenol

A flask was charged with 3-hydroxytriphenylamine (0.87 g) andN-iodosuccinimide (0.75 g) and purged with nitrogen. Anhydrousacetonitrile (16.6 mL) was degassed by purging with nitrogen, and thenadded to the reaction mixture. The reaction was stirred at roomtemperature for 1 hr. The reaction mixture was then concentrated and theresidue was then purified via chromatography on silica gel (elution with0 to 10% ethyl acetate in hexanes) to afford5-(diphenylamino)-2-iodophenol (1.13 g). ¹H NMR (400 MHz, Chloroform-d)δ 7.41 (d, 1H), 7.31-7.20 (m, 4H), 7.13-7.04 (m, 4H), 7.04 (s, 2H), 6.68(d, 1H), 6.42 (dd, 1H), 5.14 (s, 1H).

G. Synthesis of4-((4-(diphenylamino)-2-hydroxyphenyl)ethynyl)benzaldehyde

A flask was charged with 5-(diphenylamino)-2-iodophenol (0.14 g),4-ethynylbenzaldehyde (0.73 g) bis(triphenylphosphine)palladiumdichloride (0.008 g), and copper(I) iodide (0.006 g). The flask waspurged with nitrogen for 20 minutes. Tetrahydrofuran was degassed bybubbling nitrogen through for 10 minutes, then 1.86 mL added to thereaction. The reaction mixture was stirred at room temperature for 10minutes, triethylamine (0.10 mL) was added, and then the reactionstirred at room temperature for 3 hours. The reaction was heated to 50°C. for 3 hours, cooled to room temperature and then water (10 mL) andbrine (5 mL) were added. The aqueous fraction was extracted with ethylacetate (3×15 mL). The combined organic fractions were dried over sodiumsulfate, filtered, and concentrated. The residue was purified viachromatography on silica gel (elution with 0 to 25% ethyl acetate inhexanes) to afford4-((4-(diphenylamino)-2-hydroxyphenyl)ethynyl)benzaldehyde (0.094 g). ¹HNMR (400 MHz, Chloroform-d) δ 10.01 (s, 1H), 7.86 (d, 2H), 7.64 (d, 2H),7.30 (dd, 4H), 7.16-7.07 (m, 7H), 6.60-6.54 (m, 2H), 5.66 (s, 1H).

H. Synthesis of 4-(6-(Diphenylamino)benzofuran-2-yl)benzaldehyde

To a nitrogen flushed flask containing4-((4-(diphenylamino)-2-hydroxyphenyl)ethynyl)benzaldehyde (0.094 g) wasadded anhydrous toluene (4.85 mL) and tetrabutylammonium fluoride (1.0M, 0.48 mL). The reaction was heated to 80° C. for 1.5 hours then cooledto room temperature. Water (10 mL) was added and the aqueous layerextracted with ethyl acetate (3×15 mL). The combined organic fractionswere washed with brine, dried over magnesium sulfate, filtered andconcentrated to afford 4-(6-(diphenylamino)benzofuran-2-yl)benzaldehyde(0.11 g) which was used without further purification. ¹H NMR (400 MHz,DMSO-d6) δ 9.98 (s, 1H), 8.03 (d, 2H), 7.96 (d, 2H), 7.62 (d, 1H), 7.58(dd, 1H), 7.29 (dd, 4H), 7.14 (s, 1H), 7.07-7.00 (m, 6H), 6.93 (dd, 1H).

I. Synthesis of2-cyano-3-(4-(6-(diphenylamino)benzofuran-2-yl)phenyl)acrylic acid(BC-147)

To 4-(6-(diphenylamino)benzofuran-2-yl)benzaldehyde (0.048 g) was addedacetonitrile (0.61 mL), cyanoacetic acid (0.012 g), and piperidine(0.018 mL). The reaction was heated to reflux for 2.5 hours then cooledto room temperature. Water (10 mL) was added and the aqueous fractionacidified to pH=2 with 1M HCl, then extracted with dichloromethane (3×15mL). The combined organic fractions were dried over sodium sulfate,filtered, and the filtrate concentrated. The concentrated residue waspurified via chromatography on silica gel (elution with 0 to 15%methanol in dichloromethane) to afford2-cyano-3-(4-(6-(diphenylamino)benzofuran-2-yl)phenyl)acrylic acid(BC-147, 0.034 g) as a single, unidentified olefin isomer. 1H NMR (400MHz, DMSO-d6) δ 13.96 (s, 1H), 8.22 (s, 1H), 8.07 (d, 2H), 7.99 (d, 2H),7.57 (d, 2H), 7.29 (t, 4H), 7.12 (s, 1H), 7.04 (t, 6H), 6.93 (dd, 1H).Mass (m/z): 457 (M+1)+.

Example 11 Syntheses of BC-149, -152, -153, -154, -155, -160, -161, -163and -170

The compounds of this Example (and others herein) were synthesized inaccordance with Synthetic Scheme I:

A. Synthesis of Common Intermediate2-(4-(Diphenylamino)phenyl)benzofuran-6-carbaldehyde

To a 50 mL flask was added 4-ethynyltriphenylamine (1.01 g),3-hydroxy-4-iodobenzaldehyde (0.77 g), bis(triphenylphosphine)palladiumdichloride (0.066 g), and copper(I) iodide (0.054 g). The flask waspurged with nitrogen for 20 minutes. A solution of triethylamine (2.18mL) in anhydrous acetonitrile (15.6 mL) was degassed by bubblingnitrogen through for 20 minutes. The triethylamine solution was added tothe reaction and the reaction then heated to 50° C. for 3 hours. Thereaction was cooled to room temperature and water (25 mL) added. Theaqueous layer was extracted with ethyl acetate (3×30 mL) and thecombined organic fractions washed with brine and dried over sodiumsulfate. The organic layer was filtered and concentrated. The residuewas purified via chromatography on silica gel (elution with 0 to 13%ethyl acetate in hexanes) to afford2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (1.08 g). ¹H-NMR(400 MHz, DMSO-d6): δ 10.04 (s, 1H), 8.11 (d, 1H), 7.86 (d, 2H), 7.80(s, 2H), 7.42-7.34 (m, 5H), 7.17-7.10 (m, 6H), 7.03 (d, 2H).

B. 2-cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylic acid(BC-149)

Acetic acid (1.70 mL) was added to2-(4-(diphenylamino)phenyl)-benzofuran-6-carbaldehyde (0.13 g),cyanoacetic acid (0.069 g), and ammonium acetate (0.078 g) and thereaction heated to reflux for 2 hours. The reaction was cooled to roomtemperature and water (10 mL) added. The reaction was stirred at roomtemperature for one hour then the precipitate collected by filtration.The solid material was washed with water (50 mL) and hexanes (50 mL) anddried under vacuum at 50° C. to afford2-cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylic acid(BC-149, 0.14 g) as a single, unidentified olefin isomer. ¹H NMR (400MHz, DMSO-d6) δ 13.88 (broad s, 1H), 8.38 (s, 1H), 8.28 (s, 1H), 7.93(dd, J=8.4, 1.4 Hz, 1H), 7.87-7.79 (m, 2H), 7.75 (d, J=8.3 Hz, 1H),7.40-7.30 (m, 5H), 7.15-7.06 (m, 6H), 7.01-6.94 (m, 2H). Mass (m/z): 457(M+1)+.

C. 2-Cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylamide(BC-152)

To 2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.15 g) andcyanoacetamide (0.035 g) was added acetonitrile (1.9 mL) and piperidine(0.019 mL). The reaction was heated to reflux for 22 hours then cooledto room temperature. Water (10 mL) and dichloromethane (15 mL) wereadded and the aqueous layer acidified with 1M HCl. The layers wereseparated and the aqueous fraction extracted with dichloromethane (2×15mL). The combined organic layers were dried over sodium sulfate,filtered and concentrated. The residue was purified via chromatographyon silica gel (elution with 0 to 75% ethyl acetate in hexanes) to afford2-cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylamide(BC-152, 0.077 g) as a single, unidentified olefin isomer. ¹H NMR (400MHz, Chloroform-d) δ 8.41 (s, 1H), 8.20 (s, 1H), 7.77 (dd, 1H),7.75-7.69 (d, 2H), 7.60 (d, 1H), 7.35-7.26 (m, 4H), 7.18-7.06 (m, 8H),6.93 (d, 1H), 6.29 (broad s, 1H), 5.59 (broad s, 1H). Mass (m/z): 446(M+1)+.

D. (E)-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylic acid(BC-153)

To 2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.15 g) andmalonic acid (0.043 g) was added acetonitrile (1.9 mL) and piperidine(0.094 mL). The reaction was heated to reflux for 22 hours then cooledto room temperature. Water (10 mL) and dichloromethane (15 mL) wereadded and the aqueous layer acidified with 1M HCl. The layers wereseparated and the aqueous layer extracted with dichloromethane (2×15mL). The combined organic fractions were dried over sodium sulfate,filtered and concentrated to afford(E)-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylic acid (BC-153,0.166 g). ¹H NMR (400 MHz, DMSO-d6) δ 12.29 (broad s, 1H), 7.93 (s, 1H),7.78 (d, 2H), 7.66 (d, 1H), 7.62-7.52 (m, 2H), 7.37-7.29 (m, 4H), 7.26(d, 1H), 7.12-7.04 (m, 6H), 6.99 (d, 2H), 6.54 (d, J=16.0 Hz, 1H). Mass(m/z): 432 (M+1)+.

E.2-((2-(4-(Diphenylamino)phenyl)benzofuran-6-yl)methylene)malononitrile(BC-154)

To 2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.16 g) andmalononitrile (0.029 g) was added acetonitrile (2.0 mL) and piperidine(0.020 mL). The reaction was heated to reflux for 22 hours then cooledto room temperature. Water (10 mL) and dichloromethane (15 mL) wereadded and the aqueous layer acidified with 1M HCl. The layers wereseparated and the aqueous layer extracted with dichloromethane (2×15mL). The combined organic fractions were dried over sodium sulfate,filtered and concentrated. The residue was purified via chromatographyon silica gel (elution with 0 to 20% ethyl acetate in hexanes) to afford2-((2-(4-(diphenylamino)phenyl)benzofuran-6-yl)methylene)malononitrile(BC-154, 0.051 g). ¹H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.17 (s,1H), 7.88-7.77 (m, 4H), 7.39 (d, 2H), 7.35-7.31 (m, 3H), 7.17-7.07 (m,6H), 6.97 (d, 2H). Mass (m/z): 438 (M+1)+.

F. 2-((2-(4-(Diphenylamino)phenyl)benzofuran-6-yl)methylene)malonamide(BC-155)

To 2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.16 g) andmalonamide (0.046 g) was added acetonitrile (2.1 mL) and piperidine(0.020 mL). The reaction was heated to reflux for 24 hours, thenadditional malonamide (0.046 g), piperidine (0.02 mL) and1,2-dichloroethane (1.0 mL) were added and the reaction heated at refluxfor an additional 12 hours. A third portion of malonamide (0.046 g) andof piperidine (0.04 mL) was added and the reaction heated for anadditional 24 hours. The reaction was cooled to room temperature andwater (10 mL) and ethyl acetate (15 mL) were added. The reaction mixturewas stirred at room temperature for 1 hour and then the precipitatecollected by filtration. The precipitate was dried under vacuum at 60°C. to afford2-((2-(4-(diphenylamino)phenyl)benzofuran-6-yl)methylene)malonamide(BC-155, 0.64 g). ¹H NMR (400 MHz, DMSO-d6) δ 7.86 (s, 1H), 7.82-7.75(m, 3H), 7.58 (d, 1H), 7.54 (s, 1H), 7.43-7.36 (m, 2H), 7.36-7.29 (m,4H), 7.26 (broad s, 1H), 7.25 (d, 1H), 7.13 (broad s, 1H), 7.12-7.03 (m,6H), 6.98 (d, 2H). Mass (m/z): 474 (M+1)+.

G. Dimethyl2-((2-(4-(diphenylamino)phenyl)benzofuran-6-yl)methylene)malonate(BC-160)

To 2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.15 g) anddimethyl malonate (0.10 g) was added acetonitrile (1.9 mL) andpiperidine (0.038 mL). The reaction was heated to reflux for 21 hoursthen cooled to room temperature. Water (10 mL) and aqueous HCl (1M, 1.0mL) were added and the reaction extracted with ethyl acetate (3×15 mL).The combined organic was washed with aqueous NaOH (1M, 6×10 mL) andwashed with brine. The organic layer was dried over sodium sulfate,filtered, and concentrated to dimethyl2-((2-(4-(diphenylamino)phenyl)benzofuran-6-yl)methylene)malonate(BC-160, 0.11 g). ¹H NMR (400 MHz, Chloroform-d) δ 7.86 (s, 1H), 7.70(d, 2H), 7.58 (s, 1H), 7.52 (d, 1H), 7.34-7.26 (m, 5H), 7.18-7.03 (m,8H), 6.88 (s, 1H), 3.90 (s, 3H), 3.86 (s, 3H). Mass (m/z): 504 (M+1)+.

H. Methyl 2-cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylate(BC-161)

Acetic acid (1.3 mL) was added to2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.10 g), methylcyanoacetate (0.064 g), and ammonium acetate (0.062 g) and the reactionheated to reflux for 2 hours. The reaction was cooled to roomtemperature and water (10 mL) was added. The reaction was stirred atroom temperature for one hour then the precipitate collected byfiltration. The solid material was washed with water (50 mL) and hexanes(50 mL) and dried under vacuum at 50° C. to afford methyl2-cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylate (BC-161,0.12 g) as a single, unidentified olefin isomer. ¹H NMR (400 MHz,Chloroform-d) δ 8.34 (s, 1H), 8.30 (s, 1H), 7.78 (dd, 1H), 7.72 (d, 2H),7.60 (d, 1H), 7.30 (dd, 5H), 7.18-7.06 (m, 7H), 6.93 (d, 1H), 3.94 (s,3H). Mass (m/z): 471 (M+1)+.

I.2-Cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)-N-(pyridin-2-ylmethyl)acrylamide(BC-163)

To a 0° C. solution of cyanoacetic acid (0.51 g) and 2-picaloylamine(0.62 mL) in anhydrous N,N-dimethylformamide (15.1 mL) was addedN,N-diisopropylcarbodiimide (1.12 mL). The reaction was stirred at 0° C.for 10 minutes then this ice bath removed and the reaction stirred atroom temperature for 65 hours. The precipitate was removed by filtrationand the filtrate concentrated. The residue was purified viachromatography on silica gel (elution with 0 to 6% methanol indichloromethane) to afford the intermediate2-cyano-N-(pyridin-2-ylmethyl)acetamide (0.91 g). ¹H NMR (400 MHz,Chloroform-d) δ 8.56 (d, 1H), 7.69 (td, 2H), 7.51 (broad s, 1H),7.28-7.18 (m, 2H), 4.59 (d, 3H), 3.45 (s, 3H).

Acetic acid (2.0 mL) was added to2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.15 g),2-cyano-N-(pyridin-2-ylmethyl)acetamide (0.10 g), and ammonium acetate(0.091 g) and the reaction heated to reflux for 3 hours. The reactionwas cooled to room temperature and water (15 mL) added. The reaction wasstirred at room temperature for one hour then the precipitate collectedby filtration. The solid material was washed with water (50 mL) andhexanes (50 mL) and dried under vacuum at 50° C. to afford2-cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)-N-(pyridin-2-ylmethyl)acrylamide(BC-163, 0.18 g) as a single, unidentified olefin isomer. ¹H NMR (400MHz, DMSO-d6) δ 8.97 (t, 1H), 8.50 (ddd, 1H), 8.33 (s, 1H), 8.24 (s,1H), 7.91-7.79 (m, 3H), 7.78-7.69 (m, 2H), 7.41-7.29 (m, 6H), 7.26 (dd,1H), 7.16-7.05 (m, 6H), 6.99 (d, 2H), 4.51 (d, 2H). Mass (m/z): 547(M+1)+.

J. Methyl (E)-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylate(BC-170)

Acetic acid (2.7 mL) was added to 2-(4-(diphenylamino)phenyl)benzofuran-6-carbaldehyde (0.21 g), methyl potassium malonate (0.20 g),and ammonium acetate (0.12 g) and the reaction heated to reflux for 6hours. The reaction was cooled to room temperature and water (10 mL)added. The reaction was stirred at room temperature for 12 hours and theaqueous extracted with ethyl acetate (3×15 mL). The combined organic waswashed with brine, dried over sodium sulfate, filtered and concentrated.The residue was purified via chromatography on silica gel (elution with0 to 5% methanol in dichloromethane) to afford methyl(E)-3-(2-(4-(diphenylamino)phenyl)benzofuran-6-yl)acrylate (BC-170,0.056 g). ¹H NMR (400 MHz, Chloroform-d) δ 7.79 (d, 1H), 7.70 (d, 1H),7.64 (s, 1H), 7.52 (d 1H), 7.40 (dd, 1H), 7.29 (dd, 4H), 7.18-7.04 (m,9H), 6.88 (d, 1H), 6.46 (d, 1H), 3.82 (s, 3H). Mass (m/z): 446 (M+1)+.

Example 12 Syntheses of BC-167, -168 and -171

BC-167 (3-(2-(4-(tert-Butyl)phenyl)benzofuran-6-yl)-2-cyanoacrylic acid)was synthesized as shown in Synthetic Scheme I (where Z=R³).1-(R³)-4-ethynylbenzene (where R³ is tert-butyl) was condensed with3-hydroxy-4-iodobenzaldehyde, followed by addition of R²CH₂R¹ to the2-(4-(tert-butyl)phenyl)benzofuran-6-carbaldehyde.

The intermediate 2-(4-(tert-butyl)phenyl)benzofuran-6-carbaldehyde wassynthesized as follows:

To a 25 mL flask was added 3-hydroxy-4-iodobenzaldehyde (0.25 g),bis(triphenylphosphine)palladium dichloride (0.021 g), and copper(I)iodide (0.017 g). The flask was purged with nitrogen for 20 minutes. Asolution of triethylamine (0.70 mL) in anhydrous acetonitrile (5.0 mL)was degassed by bubbling nitrogen through it for 20 minutes. Thetriethylamine solution and 1-(tert-butyl)-4-ethynylbenzene (0.22 mL)were added to the reaction and this stirred at room temperature for 18hours. Water (5 mL) and ethyl acetate (5 mL) were added and the reactionstirred at room temperature for 1 hour. Water (5 mL) and 1M HCl (1 mL)were added and then the aqueous extracted with ethyl acetate (3×15 mL).The combined organic layer was washed with brine, dried over magnesiumsulfate, filtered, and concentrated. The residue was purified bychromatography on silica gel (elution with 0 to 10% ethyl acetate inhexanes) to afford 2-(4-(tert-butyl)phenyl)benzofuran-6-carbaldehyde(0.24 g). 1H NMR (400 MHz, Chloroform-d) δ 10.06 (s, 1H), 8.01 (s, 1H),7.84 (d, 2H), 7.77 (dd, 1H), 7.68 (d, 1H), 7.51 (d, 2H), 7.05 (d, 1H),1.36 (s, 9H).

BC-167 was then synthesized as follows:

Acetic acid (4.31 mL) was added to2-(4-(tert-butyl)phenyl)benzofuran-6-carbaldehyde (0.24 g), cyanoaceticacid (0.18 g), and ammonium acetate (0.20 g) and the reaction heated toreflux for 2 hours. The reaction was cooled to room temperature andwater (10 mL) added. The reaction was stirred at room temperature for 17hours and then the precipitate collected via filtration. The solidmaterial was washed with water (50 mL) and hexanes (50 mL) and driedunder vacuum at 50° C. to afford3-(2-(4-(tert-butyl)phenyl)benzofuran-6-yl)-2-cyanoacrylic acid (BC-167,0.28 g) as a single, unidentified olefin isomer. ¹H NMR (400 MHz,DMSO-d6) δ 13.88 (broad s, 1H), 8.42 (s, 1H), 8.33 (s, 1H), 7.97 (dd,1H), 7.90 (d, 2H), 7.80 (d, 1H), 7.57-7.48 (m, 3H), 1.29 (s, 9H). Mass(m/z): 346 (M+1)+.

BC-168 and -171 were also synthesized according to Synthetic Scheme I, Zis electron-donating group, X− at the 4-position of the resulting2-(4-(X)phenyl)-benzofuran-6-carbaldehyde intermediate and finalproduct.

2-Cyano-3-(2-(4-methoxyphenyl)benzofuran-6-yl)acrylic acid (BC-168) wasmade via the intermediate 2-(4-methoxyphenyl)benzofuran-6-carbaldehydeas follows:

To a 25 mL flask was added 3-hydroxy-4-iodobenzaldehyde (0.25 g),bis(triphenylphosphine)palladium dichloride (0.021 g), and copper(I)iodide (0.017 g). The flask was purged with nitrogen for 20 minutes. Asolution of triethylamine (0.70 mL) in anhydrous acetonitrile (5.0 mL)was degassed by bubbling nitrogen through for 20 minutes. Thetriethylamine solution and 1-ethynyl-4-methoxybenzene (0.16 mL) werethen added to the reaction mixture. The reaction mixture was thenstirred at room temperature for 18 hours. Water (5 mL) and ethyl acetate(5 mL) were added and the reaction stirred at room temperature for 1hour. Water (5 mL) and 1M HCl (1 mL) were added and then the aqueouslayer extracted with ethyl acetate (3×15 mL). The combined organicfractions were washed with brine, dried over magnesium sulfate,filtered, and the filtrate concentrated. The residue was purified viachromatography on silica gel (elution with 0 to 15% ethyl acetate inhexanes) to afford 2-(4-methoxyphenyl)benzofuran-6-carbaldehyde (0.25g). 1H NMR (400 MHz, Chloroform-d) δ 10.05 (s, 1H), 7.99 (s, 1H), 7.84(d, 2H), 7.76, (dd, 1H), 7.65 (d, 1H), 7.01 (d, 2H), 6.95 (d, 1H), 3.88(s, 3H).

The final product BC-168 was derived from the intermediate as follows:

Acetic acid (4.87 mL) was added to2-(4-methoxyphenyl)benzofuran-6-carbaldehyde (0.25 g), cyanoacetic acid(0.20 g), and ammonium acetate (0.23 g) and the reaction heated toreflux for 2 hours. The reaction was cooled to room temperature andwater (10 mL) added. The reaction was stirred at room temperature for 17hours and then the precipitate collected by filtration. The solidmaterial was washed with water (50 mL) and hexanes (50 mL) and driedunder vacuum at 50° C. to afford2-cyano-3-(2-(4-methoxyphenyl)benzofuran-6-yl)acrylic acid (BC-168, 0.27g) as a single, unidentified olefin isomer. ¹H NMR (400 MHz, DMSO-d6) δ13.85 (s, 1H), 8.41 (s, 1H), 8.31 (s, 1H), 7.98-7.88 (m, 3H), 7.77 (d,1H), 7.42 (d, 1H), 7.07 (d, 2H), 3.81 (s, 3H). Mass (m/z): 320 (M+1)+.

2-Cyano-3-(2-(4-phenoxyphenyl)benzofuran-6-yl)acrylic acid (BC-171) wasmade via the intermediate 2-(4-phenoxyphenyl)benzofuran-6-carbaldehydeas follows:

To a 25 mL flask was added 3-hydroxy-4-iodobenzaldehyde (0.25 g),bis(triphenylphosphine)palladium dichloride (0.021 g), and copper(I)iodide (0.017 g). The flask was purged with nitrogen for 20 minutes. Asolution of triethylamine (0.70 mL) in anhydrous acetonitrile (5.0 mL)was degassed by bubbling nitrogen through for 20 minutes. Thetriethylamine solution and 1-ethynyl-4-phenoxybenzene (0.22 mL) wereadded to the reaction and this heated to 40° C. for 2.5 hours. Thereaction was cooled to room temperature and water (5 mL) and 1M HCl (1mL) added. The aqueous was extracted with ethyl acetate (3×15 mL) andthe combined organic layer was washed with brine, dried over magnesiumsulfate, filtered, and concentrated. The residue was purified viachromatography on silica gel (elution with 0 to 13% ethyl acetate inhexanes) to afford 2-(4-phenoxyphenyl)benzofuran-6-carbaldehyde (0.25g). ¹H NMR (400 MHz, Chloroform-d) δ 10.06 (s, 1H), 8.00 (s, 1H), 7.86(d, 2H), 7.78 (dd, 1H), 7.67 (d, 1H), 7.39 (dd, 2H), 7.18 (d, 1H),7.12-7.05 (m, 4H), 7.00 (d, 1H).

The final product BC-171 was derived from the intermediate as follows:

Acetic acid (3.98 mL) was added to2-(4-phenoxyphenyl)benzofuran-6-carbaldehyde (0.25 g), cyanoacetic acid(0.16 g), and ammonium acetate (0.18 g) and the reaction heated toreflux for 2 hours. The reaction was cooled to room temperature andwater (10 mL) added. The reaction was stirred at room temperature for 1hour and then the precipitate collected via filtration. The solidmaterial was washed with water (50 mL) and hexanes (50 mL) and driedunder vacuum at 50° C. to afford2-cyano-3-(2-(4-phenoxyphenyl)benzofuran-6-yl)acrylic acid (BC-171, 0.28g) as a single, unidentified olefin isomer. ¹H NMR (400 MHz, DMSO-d6) δ13.87 (s, 1H), 8.42 (s, 1H), 8.32 (s, 1H), 8.06-7.90 (m, 3H), 7.80 (d),7.49 (d, 1H), 7.47-7.36 (m, 2H), 7.19 (t, 1H), 7.13-7.04 (m, 4H). Mass(m/z): 382 (M+1)+.

Example 13 Synthetic Scheme II—Synthesis of BC-151 Synthetic Scheme II

2-Cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-5-yl)acrylic acid(BC-151) was synthesized according to Synthetic Scheme II, starting withcondensation of 4-(Z)ethynylbenzene (where Z=diphenylamine) with3-bromo-4-hydroxybenzaldehyde to form the2-(4-(Z)phenyl)benzofuran-5-carbaldehyde, followed by addition ofR²CH₂R¹ to the carbaldehyde.

BC-151 was made via the intermediate2-(4-(diphenylamino)phenyl)-benzofuran-5-carbaldehyde as follows:

To a nitrogen filled flask was added 4-ethynyl-N,N-diphenylaniline (0.49g), 3-bromo-4-hydroxybenzaldehyde (0.30 g),bis(triphenylphosphine)palladium dichloride (0.032 g), and copper(I)iodide (0.026 g) and the flask was purged with nitrogen for 20 minutes.Degassed 1,4-dioxane (7.5 mL) and N,N-diisopropylethylamine (1.3 mL)were added to the reaction and the reaction heated to 80° C. for 2hours. The reaction temperature was increased to 100° C. for 22 hours.The reaction mixture was cooled to room temperature and water (10 mL)and brine (10 mL) were added. The aqueous layer was extracted with ethylacetate (3×30 mL) and the combined organic layers dried over magnesiumsulfate, filtered, and concentrated. The residue was purified viachromatography on silica gel (elution with 0 to 10% ethyl acetate inhexanes) to afford 2-(4-(diphenylamino)phenyl)benzofuran-5-carbaldehyde(0.24 g). ¹H NMR (400 MHz, Chloroform-d) δ 10.04 (s, 1H), 7.98 (s, 1H),7.78-7.71 (m, 3H), 7.64 (d, 2H), 7.33-7.27 (m, 4H), 7.18-7.06 (m, 7H),6.94 (d, 1H).

The final product BC-151 was derived from the intermediate as follows:

To 2-(4-(diphenylamino)phenyl)benzofuran-5-carbaldehyde (0.24 g) wasadded acetonitrile (3.0 mL), cyanoacetic acid (0.057 g), and piperidine(0.090 mL). The reaction was heated to reflux for 3 hours then cooled toroom temperature. Water (10 mL) and dichloromethane (20 mL) were addedand the aqueous acidified to pH=2 with 1M HCl. The layers were separatedand the aqueous extracted with dichloromethane (2×20 mL). The combinedorganic was washed with brine, dried over sodium sulfate, filtered, andconcentrated. The residue was purified via chromatography on silica gel(elution with 0 to 15% methanol in dichloromethane) to provide2-cyano-3-(2-(4-(diphenylamino)phenyl)benzofuran-5-yl)acrylic acid(BC-151, 0.14 g) as a single, unidentified olefin isomer. ¹H NMR (400MHz, DMSO-d6) δ 13.96 (broad s, 1H), 8.38 (s, 1H), 8.31 (s, 1H), 7.95(d, 1H), 7.78 (t, 3H), 7.39 (s, 1H), 7.33 (t, 4H), 7.09 (dd, 6H), 6.99(d, 2H). Mass (m/z): 457 (M+1)+.

Example 14 Synthetic Scheme III—Syntheses of BC-156, -157, -158, -159and -175 Synthetic Scheme III

Products BC-156, -157, -158, -159 and -175, were all synthesizedaccording to Synthetic Scheme III. First, 1-bromo-4-ethynylbenzene wascondensed with 3-hydroxy-4-iodobenzaldehyde in the presence of acatalyst (bis(triphenylphosphine)-palladium dichloride/copper(I) iodidein acetonitrile) and proton scavenger (triethylamine) to formintermediate 2-(4-bromophenyl)benzofuran-6-carbaldehyde. Theintermediate was then condensed with R′(R″)′N to form2-(4-(R′(R″)amino)phenyl)-benzofuran-6-carbaldehyde which was followedby addition of R²CH₂R¹ to form each of the BC products.

A. Synthesis of intermediate 2-(4-bromophenyl)benzofuran-6-carbaldehyde

To a 100 mL flask was added 1-bromo-4-ethynylbenzene (1.75 g),3-hydroxy-4-iodobenzaldehyde (2.00 g), bis(triphenylphosphine)palladiumdichloride (0.17 g), and copper(I) iodide (0.14 g). The flask was purgedwith nitrogen for 20 minutes. A solution of triethylamine (5.62 mL) inanhydrous acetonitrile (40.3 mL) was degassed by bubbling nitrogenthrough for 20 minutes. The degassed triethylamine solution was added tothe reaction and the reaction heated to 40° C. for 1.5 hours. Thereaction was cooled to room temperature and concentrated. The residuewas purified via chromatography on silica gel (elution with 0 to 25%ethyl acetate in hexanes) to afford2-(4-bromophenyl)benzofuran-6-carbaldehyde (2.50 g). ¹H NMR (400 MHz,Chloroform-d) δ 10.07 (s, 1H), 8.01 (s, 1H), 7.86-7.74 (m, 3H), 7.70 (d,1H), 7.66-7.56 (m, 2H), 7.10 (d, 1H).

B. Synthesis of intermediate,2-(4-(bis(4-methoxyphenyl)amino)phenyl)-benzofuran-6-carbaldehyde

A 10 mL flask containing 2-(4-bromophenyl)benzofuran-6-carbaldehyde(0.053 g), bis(4-methoxyphenyl)amine (0.041 g),tris(dibenzylideneacetone)dipalladium (0.0041 g), QPhos (0.0063 g), andsodium tert-butoxide (0.026 g) was purged with nitrogen for 20 minutes.Anhydrous toluene (0.89 mL) was degassed by bubbling nitrogen throughfor 20 minutes then added to the reaction. The reaction was stirred atroom temperature for 2.5 hours and quenched by the addition of water (10mL). The aqueous was extracted with ethyl acetate (3×15 mL) and thecombined organic dried over magnesium sulfate. The organic layer wasfiltered and concentrated. The residue was purified via chromatographyon silica gel (elution with 0 to 20% ethyl acetate in hexanes) to afford2-(4-(bis(4-methoxyphenyl)amino)phenyl)benzofuran-6-carbaldehyde (0.046g). ¹H NMR (400 MHz, Chloroform-d) δ 10.03 (s, 1H), 7.96 (s, 1H), 7.74(dd, 1H), 7.66 (d, 2H), 7.61 (d, 1H), 7.10 (dd, 4H), 6.95 (dd, 2H),6.89-6.83 (m, 5H), 3.81 (s, 6H).

C. Synthesis of3-(2-(4-(Bis(4-methoxyphenyl)amino)phenyl)benzofuran-6-yl)-2-cyanoacrylicacid (BC-156) and3-(2-(4-(Bis(4-methoxyphenyl)amino)phenyl)-benzofuran-6-yl)acrylonitrile(BC-157)

To a solution of2-(4-(bis(4-methoxyphenyl)amino)phenyl)benzofuran-6-carbaldehyde (0.20g) and cyanoacetic acid (0.042 g) in acetonitrile (2.27 mL) was addedpiperidine (0.067 mL). The reaction was heated to reflux for 24 hours.Additional cyanoacetic acid (0.042 g) and piperidine (0.067 mL) wereadded and the reaction heated at reflux for an additional 4 hours. Thereaction was cooled to room temperature and water (10 mL) anddichloromethane (20 mL) were added. The aqueous layer was acidified topH=2 with 1M HCl and the layers separated. The aqueous fraction wasextracted with dichloromethane (2×15 mL) and the combined organicfractions dried over sodium sulfate, filtered and concentrated. Theresidue was purified via column chromatography (0 to 15% methanol indichloromethane) to afford impure BC-156 and impure BC-157. BC-156 wasfurther purified via column chromatography on silica gel (1^(st) column:elution with 0 to 10% methanol in dichloromethane; 2^(nd) column:elution with 0 to 100% ethyl acetate in hexanes, then 0 to 20% methanolin dichloromethane) to afford3-(2-(4-(bis(4-methoxyphenyl)amino)phenyl)benzofuran-6-yl)-2-cyanoacrylicacid (BC-156, 0.037 g) as a single, unidentified olefin isomer. Theimpure BC-157 was further purified via column chromatography on silicagel (elution with 0 to 20% ethyl acetate in hexanes) to afford3-(2-(4-(bis(4-methoxyphenyl)amino)phenyl)benzofuran-6-yl)acrylonitrile(BC-157, 0.064 g) as an approximately 5:1 mixture of E:Z olefin isomers.

BC-156: ¹H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 8.01 (broad s, 1H),7.72 (d, 3H), 7.63 (d, 1H), 7.21 (s, 1H), 7.08 (dd, 4H), 6.92 (dd, 4H),6.76 (dd, 2H), 3.72 (s, 6H). Mass (m/z): 517 (M+1)+. BC-157, majorisomer (E isomer): ¹H NMR (400 MHz, Chloroform-d) δ 7.69-7.56 (m, 2H),7.54 (s, 1H), 7.50 (d, 1H), 7.47 (d, 1H), 7.29 (dd, 1H), 7.14-7.05 (m,4H), 6.94 (dd, 2H), 6.90-6.79 (m, 5H), 5.85 (d, J=16.6 Hz, 1H), 3.81 (s,6H). Mass (m/z): 473 (M+1)+.

D. Synthesis of intermediate2-(4-(bis(4-(tert-butyl)phenyl)amino)phenyl)-benzofuran-6-carbaldehyde

A 10 mL flask containing 2-(4-bromophenyl)benzofuran-6-carbaldehyde(0.21 g), bis(4-(tert-butyl)phenyl)amine (0.19 g),tris(dibenzylideneacetone)dipalladium (0.016 g), QPhos (0.024 g), andsodium tert-butoxide (0.099 g) was purged with nitrogen for 20 minutes.Anhydrous toluene (3.43 mL) was degassed by bubbling nitrogen throughfor 20 minutes then added to the reaction. The reaction was stirred atroom temperature for 3 hours and quenched by the addition of water (15mL) and 1M HCl (1.02 mL). The aqueous was extracted with ethyl acetate(3×20 mL) and the combined organic fractions dried over magnesiumsulfate, filtered and concentrated. The residue was purified viachromatography on silica gel (elution with 0 to 10% ethyl acetate inhexanes) to afford2-(4-(bis(4-(tert-butyl)phenyl)amino)phenyl)benzofuran-6-carbaldehyde(0.20 g). ¹H NMR (400 MHz, Chloroform-d) δ 10.03 (s, 1H), 7.97 (s, 1H),7.75 (dd, 1H), 7.70 (d, 2H), 7.62 (d, 1H), 7.30 (d, 4H), 7.07 (dd, Hz,6H), 6.91 (d, 1H), 1.32 (s, 18H).

E. Synthesis of3-(2-(4-(Bis(4-(tert-butyl)phenyl)amino)phenyl)benzofuran-6-yl)-2-cyanoacrylicacid (BC-158)

Acetic acid (0.49 mL) was added to2-(4-(bis(4-(tert-butyl)phenyl)amino)phenyl)benzofuran-6-carbaldehyde(0.049 g), cyanoacetic acid (0.020 g), and ammonium acetate (0.023 g)and the reaction heated to reflux for 1.5 hours. The reaction was cooledto room temperature and water (10 mL) added. The reaction was stirred atroom temperature for 2 hours then the precipitate collected byfiltration. The solid material was washed with water (50 mL) and hexanes(50 mL) and dried under vacuum at 50° C. to afford3-(2-(4-(bis(4-(tert-butyl)phenyl)amino)phenyl)benzofuran-6-yl)-2-cyanoacrylicacid (BC-158, 0.049 g) as a single, unidentified olefin isomer. ¹H NMR(400 MHz, DMSO-d6) δ 8.38 (s, 1H), 8.28 (s, 1H), 7.93 (d, 1H), 7.80 (d,2H), 7.74 (d, 1H), 7.40-7.29 (m, 5H), 7.02 (d, 4H), 6.90 (d, 2H), 1.25(s, 18H). Mass (m/z): 569 (M+1)+.

F. Synthesis of2-Cyano-3-(2-(4-(di(pyridin-3-yl)amino)phenyl)benzofuran-6-yl)acrylicacid (BC-159)

The intermediate di(pyridin-3-yl)amine:

was synthesized by a procedure adapted from WO2007089735A2. A 25 mLflask containing 3-aminopyridine (0.30 g), 3-iodopyridine (0.99 g),tris(dibenzylideneacetone)dipalladium (0.0291 g), Xantphos (0.084 g),and sodium tert-butoxide (0.37 g) was purged with nitrogen for 20minutes. Anhydrous toluene (6.41 mL) was degassed by bubbling nitrogenthrough for 20 minutes and then added to the reaction. The reaction washeated to 50° C. for 24 hours and then cooled to room temperature. Thereaction mixture was diluted with dichloromethane (100 mL) and thenwashed with water (20 mL) and brine (20 mL). The organic layer was driedover sodium sulfate, filtered, and concentrated. The residue waspurified via chromatography on silica gel (elution with 0 to 10%methanol in dichloromethane) to afford di(pyridin-3-yl)amine (0.54 g).¹H NMR (400 MHz, Chloroform-d) δ 8.41 (d, J=2.8 Hz, 2H), 8.23 (dd,J=4.7, 1.3 Hz, 2H), 7.41 (ddd, J=8.2, 2.5, 1.2 Hz, 2H), 7.21 (dd, J=8.3,4.8 Hz, 2H), 5.81 (broad s, 1H).

Next the intermediate2-(4-(di(pyridin-3-yl)amino)phenyl)benzofuran-6-carbaldehyde wassynthesized as follows:

A 10 mL flask containing 2-(4-bromophenyl)benzofuran-6-carbaldehyde(0.19 g), di(pyridin-3-yl)amine (0.11 g),tris(dibenzylideneacetone)dipalladium (0.014 g), QPhos (0.022 g), andsodium tert-butoxide (0.089 g) was purged with nitrogen for 30 minutes.Anhydrous toluene (3.1 mL) was degassed by bubbling nitrogen through for30 minutes then added to the reaction. The reaction was stirred at roomtemperature for 3 hours and quenched by the addition of water (15 mL).The aqueous was extracted with dichloromethane (3×15 mL) and thecombined organic fractions dried over magnesium sulfate, filtered andconcentrated. The residue was purified via chromatography on silica gel(elution with 0 to 5% methanol in dichloromethane) to afford2-(4-(di(pyridin-3-yl)amino)phenyl)benzofuran-6-carbaldehyde (0.096 g).¹H NMR (400 MHz, Chloroform-d) δ 10.05 (s, 1H), 8.45 (d, 2H), 8.36 (dd,2H), 8.00 (s, 1H), 7.84-7.79 (m, 2H), 7.77 (dd, 1H), 7.67 (d, 1H), 7.46(ddd, 2H), 7.25 (m, 2H), 7.15 (d, 2H), 7.01 (d, 1H).

The final product2-cyano-3-(2-(4-(di(pyridin-3-yl)amino)phenyl)-benzofuran-6-yl)acrylicacid (BC-159) was synthesized:

Acetic acid (1.04 mL) was added to2-(4-(di(pyridin-3-yl)amino)phenyl)benzofuran-6-carbaldehyde (0.096 g),cyanoacetic acid (0.043 g), and ammonium acetate (0.048 g) and thereaction heated to reflux for 2.5 hours. The reaction was cooled to roomtemperature and water (10 mL) added. The reaction was stirred at roomtemperature for 0.5 hours then the precipitate collected via filtration.The solid material was washed with water (50 mL) and hexanes (50 mL) anddried under vacuum at 50° C. The material was purified viachromatography on silica gel (elution with 0 to 20% methanol indichloromethane) to afford2-cyano-3-(2-(4-(di(pyridin-3-yl)amino)phenyl)benzofuran-6-yl)acrylicacid (BC-159, 0.066 g) as a single, unidentified olefin isomer. ¹H NMR(400 MHz, DMSO-d6) δ 8.35 (d, 2H), 8.33 (dd, 2H), 8.21 (s, 1H), 8.17(broad s, 1H), 7.91 (d, 2H), 7.84 (d, 1H), 7.73 (d, 1H), 7.55 (ddd, 2H),7.42 (s, 1H), 7.38 (dd, 2H), 7.09 (d, 2H). Mass (m/z): 459 (M+1)+.

G. Synthesis of2-cyano-3-(2-(4-(methyl(phenyl)amino)phenyl)benzofuran-6-yl)acrylic acid(BC-175)

First, the intermediate2-(4-(methyl(phenyl)amino)phenyl)benzofuran-6-carbaldehyde was made asfollows:

A 10 mL flask containing 2-(4-bromophenyl)benzofuran-6-carbaldehyde(0.19 g), tris(dibenzylideneacetone)dipalladium (0.014 g), QPhos (0.022g), and sodium tert-butoxide (0.089 g) was purged with nitrogen for 30minutes. Anhydrous toluene (3.1 mL) was degassed by bubbling nitrogenthrough for 30 minutes. The degassed toluene and N-methylaniline (0.07mL) were added to the flask. The reaction mixture was stirred at roomtemperature for 1 hour and quenched by the addition of water (10 mL) and1M HCl (1 mL). The aqueous layer was extracted with ethyl acetate (3×15mL) and the combined organic fractions washed with brine and dried overmagnesium sulfate, filtered and concentrated. The residue was purifiedvia chromatography on silica gel (elution with 0 to 15% ethyl acetate inhexanes) to afford 2-(4-(methyl(phenyl)amino)phenyl)benzofuran-6-carbaldehyde (0.12 g). ¹H NMR (400 MHz, Chloroform-d) δ10.03 (s, 1H), 7.97 (s, 1H), 7.77-7.71 (m, 3H), 7.62 (d, 1H), 7.38 (dd,2H), 7.20 (dd, 2H), 7.18-7.12 (m, 1H), 6.94 (d, 2H), 6.89 (d, 1H), 3.39(s, 3H).

The final product BC-175 was made from the intermediate as follows:

Acetonitrile (1.92 mL) and piperidine (0.076 mL) were added to2-(4-(methyl(phenyl)amino)phenyl)benzofuran-6-carbaldehyde (0.12 g) andcyanoacetic acid (0.049 g). The reaction heated to reflux for 2 hours.The reaction was cooled to room temperature and water (10 mL) and aceticacid (1 mL) were added. The reaction was stirred at room temperature for4 hours then the precipitate collected by filtration. The solid materialwas washed with water (50 mL) and hexanes (50 mL) and dried under vacuumat 50° C. to afford2-cyano-3-(2-(4-(methyl(phenyl)amino)phenyl)benzofuran-6-yl)acrylic acid(BC-175, 0.135 g) as a single, unidentified olefin isomer. ¹H NMR (400MHz, DMSO-d6) δ 13.9 (broad s, 1H), 8.37 (s, 1H), 8.27 (s, 1H), 7.92 (d,1H), 7.84-7.76 (m, 2H), 7.72 (d, 1H), 7.42-7.35 (m, 2H), 7.30 (d, 1H),7.21 (dd, 2H), 7.15 (t, 1H), 6.96-6.88 (d, 2H), 3.32 (s, 3H). Mass(m/z): 395 (M+1)+.

Example 15 Synthesis of BC-166, -169, -172 and -173

Final products BC-166, -169, -172 and -173, were synthesized from2-(4-bromophenyl)benzofuran-6-carbaldehyde (synthesized in Example 14Aabove). For these molecules, the carbaldehyde was protected as theacetal prior to its reaction with a secondary amine, as shown inSynthetic Scheme IV, in which addition of a cyclic secondary amine tothe acetal is shown (for illustrative purposes). The condensation withamine is followed by deprotection of the carbaldehyde and its reactionwith R²CH₂R¹ (as in Synthetic Scheme I).

Synthetic Scheme IV

A. Synthesis of common intermediate2-(4-Bromophenyl)-6-(diethoxymethyl)-benzofuran

To a nitrogen flushed flask containing2-(4-bromophenyl)benzofuran-6-carbaldehyde (1.0 g) was addedp-toluenesulfonic acid monohydrate (0.063 g), ethanol (200 proof, 8.3mL), ethyl acetate (8.3 mL) and triethylorthoformate (5.5 mL). Thereaction was stirred at room temperature for 22 hours. Toluene (15 mL)was added and the reaction concentrated. Toluene (15 mL) was again addedand the reaction again concentrated to afford2-(4-bromophenyl)-6-(diethoxymethyl)benzofuran which was used withoutfurther purification. ¹H NMR (400 MHz, DMSO-d6) δ 7.84 (d, 2H), 7.68 (d,2H), 7.62 (d, 1H), 7.58 (s, 1H), 7.48 (d, 1H), 7.29 (dd, 1H), 5.57 (s,1H), 3.57-3.42 (m, 4H), 1.13 (t, 6H).

B. Synthesis of2-Cyano-3-(2-(4-(piperidin-1-yl)phenyl)benzofuran-6-yl)acrylic acid(BC-166)

First, the intermediate2-(4-(Piperidin-1-yl)phenyl)benzofuran-6-carbaldehyde was made asfollows:

A 10 mL flask containing the2-(4-bromophenyl)-6-(diethoxymethyl)benzofuran (0.075 g),tris(dibenzylideneacetone)dipalladium (0.005 g),tri-tert-butylphosphonium tetrafluoroborate (0.003 g), and sodiumtert-butoxide(0.029 g) was purged with nitrogen for 20 minutes.Anhydrous toluene (0.40 mL) was degassed by bubbling nitrogen throughfor 20 minutes then added to the reaction. Piperidine (0.024 mL) wasadded and the reaction heated to 80° C. for 2 hours and then cooled toroom temperature. Ethyl acetate (10 mL) and 1M HCl (10 mL) were addedand the reaction stirred at room temperature for 1.5 hours. The aqueouslayer was neutralized with saturated sodium bicarbonate and extractedwith ethyl acetate (3×15 mL). The combined organic fractions were washedwith brine, dried over magnesium sulfate, filtered and the filtrateconcentrated. The residue was purified via chromatography on silica gel(elution with 0 to 10% ethyl acetate in hexanes) to afford2-(4-(piperidin-1-yl)phenyl)benzofuran-6-carbaldehyde (0.044 g). ¹H NMR(400 MHz, Chloroform-d) δ 10.03 (s, 1H), 7.96 (s, 1H), 7.81-7.71 (m,3H), 7.61 (d, J=7.9 Hz, 1H), 6.97 (d, J=7.9 Hz, 2H), 6.88 (s, 1H),3.36-3.24 (m, 4H), 1.68 (d, J=29.2 Hz, 6H).

The final product BC-166 was then made as follows:

Acetic acid (1.51 mL) was added to2-(4-(piperidin-1-yl)phenyl)benzofuran-6-carbaldehyde (0.092 g),cyanoacetic acid (0.062 g), and ammonium acetate (0.070 g) and thereaction heated to reflux for 2.5 hours. The reaction was cooled to roomtemperature and water (20 mL) added. The reaction was stirred at roomtemperature for 1.5 hours then the precipitate collected by filtration.The solid material was washed with water (50 mL) and then with hexanes(50 mL) and then dried under vacuum at 50° C. to afford2-cyano-3-(2-(4-(piperidin-1-yl)phenyl)benzofuran-6-yl)acrylic acid(BC-166, 0.090 g) as a single, unidentified olefin isomer. ¹H NMR (400MHz, DMSO-d6) δ 8.35 (s, 1H), 8.25 (s, 1H), 7.91 (dd, 1H), 7.77 (d, 2H),7.70 (d, 1H), 7.27 (d, 1H), 7.01 (d, 2H), 3.30 (broad s, 4H), 1.56(broad s, 6H). Mass (m/z): 373 (M+1)+.

C. Synthesis of 2-Cyano-3-(2-(4-morpholinophenyl)benzofuran-6-yl)acrylicacid (BC-169

First the intermediate 2-(4-Morpholinophenyl)benzofuran-6-carbaldehydewas made as follows:

To 2-(4-bromophenyl)-6-(diethoxymethyl)benzofuran (0.309 g, 0.824 mmol)was added tris(dibenzylideneacetone)dipalladium(0) (19 mg),tri(tert-butyl)phosphine tetrafluoroborate (12 mg) and sodiumtert-butoxide (118 mg). The reaction mixture was purged with nitrogenfor 20 minutes. Dry toluene (3 mL) was degassed by purging with nitrogenfor 20 minutes and then added to the reaction mixture. Morpholine (0.086mL) was added and the reaction mixture was heated to 80° C. After 4 h,the reaction was cooled to room temperature, and 1 M HCl (10 mL) andethyl acetate (10 mL) was added. The mixture was stirred at roomtemperature for 1.5 h. The reaction mixture was then neutralized withsaturated sodium bicarbonate, extracted with ethyl acetate (3×15 mL),dried over sodium sulfate, filtered and concentrated. The solid waspurified by silica gel column, eluting with hexanes:ethyl acetate (ethylacetate as a gradient from 0 to 50%) to afford2-(4-morpholinophenyl)-benzofuran-6-carbaldehyde (135 mg, 53%). ¹H-NMR(400 MHz, CDCl3): δ 10.03 (s, 1H), 7.96 (s, 1H), 7.80 (d, 2H), 7.74 (dd,1H), 7.62 (d, 1H), 6.99 (d, 2H), 6.91 (d, 1H), 3.88 (t, 4H), 3.26 (t,4H). Mass (m/z): 308 (M+1)+.

The final product BC-169 was then made by reaction of2-(4-morpholinophenyl)benzofuran-6-carbaldehyde with cyanoacetic acid inacetic acid in the presence of ammonium acetate (similarly to themethods described for synthesis of BC-166 from its correspondingaldehyde in Example 15B):

The yield was 143 mg. ¹H NMR (400 MHz, DMSO-d6): δ 8.40 (s, 1H), 8.28(s, 1H), 7.95 (dd, 1H), 7.82 (d, 2H), 7.73 (d, 1H), 7.33 (s, 1H), 7.05(d, 2H), 3.73 (t, 4H), 3.22 (t, 4H). Mass (m/z): 375 (M+1)+.

D. Synthesis of2-Cyano-3-(2-(4-(4-methylpiperazin-1-yl)phenyl)benzofuran-6-yl)acrylicacid (BC-172)

First, intermediate2-(4-(4-Methylpiperazin-1-yl)phenyl)benzofuran-6-carbaldehyde was made

similarly to the methods described for synthesis of2-(4-morpholinophenyl)benzofuran-6-carbaldehyde in Example 15C. Theyield was 153 mg (58%). ¹H NMR (400 MHz, DMSO-d6): δ 8.27 (s, 1H), 8.23(s, 1H), 7.88 (dd, 1H), 7.83 (d, 2H), 7.71 (d, 1H), 7.32 (s, 1H), 7.09(d, 2H), 3.42 (br s, 4H), 2.88 (br s, 4H), 2.49 (s, 3H). Mass (m/z): 388(M+1)+.

The final product BC-172 was made

similar to the methods described for synthesis of BC-166 Example 15B,yield 64 mg, 70%. ¹H-NMR (400 MHz, CDCl3): δ 10.02 (s, 1H), 7.95 (s,1H), 7.78 (d, 2H), 7.73 (dd, 1H), 7.61 (d, 1H), 6.98 (d, 2H), 6.89 (d,1H), 3.35 (t, 4H), 2.64 (t, 4H), 2.40 (s, 3H). Mass (m/z): 321 (M+1)+.

E. Synthesis of2-Cyano-3-(2-(4-(diethylamino)phenyl)benzofuran-6-yl)acrylic acid(BC-173)

First, intermediate 2-(4-(Diethylamino)phenyl)benzofuran-6-carbaldehydewas made as follows:

A 10 mL flask containing the2-(4-bromophenyl)-6-(diethoxymethyl)benzofuran (0.22 g),tris(dibenzylideneacetone)dipalladium (0.013 g),tri-tert-butylphosphonium tetrafluoroborate (0.008 g), and sodiumtert-butoxide (0.083 g) was purged with nitrogen for 20 minutes.Anhydrous toluene (1.2 mL) was degassed by bubbling nitrogen through for20 minutes then added to the reaction. Diethylamine (0.12 mL) was addedand the reaction heated to 80° C. for 2 hours and then cooled to roomtemperature. Ethyl acetate (5 mL) and 1M HCl (5 mL) were added and thereaction stirred at room temperature for 1 hour. The aqueous layer wasneutralized with saturated sodium bicarbonate and extracted with ethylacetate (3×15 mL). The combined organic fractions were washed withbrine, dried over magnesium sulfate, filtered and concentrated. Theresidue was purified via chromatography on silica gel (elution with 0 to10% ethyl acetate in hexanes) to afford2-(4-(diethylamino)phenyl)-benzofuran-6-carbaldehyde (0.097 g). ¹H NMR(400 MHz, DMSO-d6) δ 9.98 (s, 1H), 8.02 (s, 1H), 7.78-7.70 (m, 3H), 7.68(d, 1H), 7.19 (d, 1H), 6.75 (d, 2H), 3.39 (q, 4H), 1.10 (t, 6H).

The final product BC-173 was then made as follows:

To 2-(4-(diethylamino)phenyl)benzofuran-6-carbaldehyde (0.097 g) andcyanoacetic acid (0.031 g) was added acetonitrile (1.6 mL) andpiperidine (0.049 mL). The reaction was heated to reflux for 2 hoursthen additional cyanoacetic acid (0.006 g) was added. After anadditional 2 hours, additional cyanoacetic acid (0.006 mg) andpiperidine (0.024 mL) were added and the reaction heated at reflux for20 hours. The reaction was cooled to room temperature, then water (10mL) and acetic acid (1.0 mL) were added and the reaction stirred at roomtemperature for 2 hours. The precipitate was collected by filtration andwashed with water (50 mL) and hexanes (50 mL). The solid was dried undervacuum at 50° C. to afford2-cyano-3-(2-(4-(diethylamino)phenyl)-benzofuran-6-yl)acrylic acid(BC-173, 0.098 g) as a single, unidentified olefin isomer. ¹H NMR (400MHz, DMSO-d6) δ 13.76 (s, 1H), 8.38 (s, 1H), 8.25 (s, 1H), 7.91 (dd,1H), 7.74 (d, 2H), 7.68 (d, 1H), 7.19 (d, 1H), 6.75 (d, 2H), 3.39 (q,4H), 1.10 (t, 6H). Mass (m/z): 361 (M+1)+.

Example 16 Synthesis of BC-162 and BC-165

BC-162 and BC-165 were also synthesized from2-(4-bromophenyl)benzofuran-6-carbaldehyde (synthesized in Example 14Aabove).

A. Synthesis of 3-(2-(4-bromophenyl)benzofuran-6-yl)-2-cyanoacrylic acid(BC-162)

2-(4-Bromophenyl)benzofuran-6-carbaldehyde was converted to3-(2-(4-bromophenyl)benzofuran-6-yl)-2-cyanoacrylic acid (BC-162) byreaction with cyanoacetic acid and ammonium acetate, similarly to themethods used for the synthesis of BC-166 in Example 15B, with a yield of232 mg, 98%. ¹H NMR (400 MHz, DMSO-d6): δ 8.27 (s, 1H), 8.26 (s, 1H),7.94 (d, J=8.8 Hz, 2H), 7.90 (d, J=1.5 Hz, 1H), 7.80 (d, J=8.32 Hz, 1H),7.73 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 7.22 (br s, 1H). Mass (m/z): 367(M−1)−.

B. Synthesis of2-Cyano-3-(2-(3′,4′-dimethoxy-[1,1′-biphenyl]-4-yl)benzofuran-6-yl)acrylicacid (BC-165)

First, the intermediate2-(3′,4′-Dimethoxy-[1,1′-biphenyl]-4-yl)benzofuran-6-carbaldehyde wasmade as follows:

A round bottom flask (10 mL) was charged with2-(4-bromophenyl)benzofuran-6-carbaldehyde (155 mg, 0.5 mmol), 3,4-dimethoxy phenyl boronic acid (100 mg, 0.5 mmol), and PdCl₂(PPh₃)₂(17mg), and then purged with nitrogen for 20 minutes. 1,2-Dimethoxyethanewas degassed by bubbling nitrogen for 20 minutes. 1,2-Dimethoxyethane(3.5 mL) was added to the reaction, followed by the addition oftriethylamine (101 mg) and stirred at 90° C. under nitrogen overnight.The reaction mixture was cooled to room temperature and the solvent wasremoved under vacuum. The solid was purified by silica gel column(hexanes with ethyl acetate from 0 to 30%) to afford2-(3′,4′-dimethoxy-[1,1′-biphenyl]-4-yl)benzofuran-6-carbaldehyde (88mg, 49%) as light yellow solid. ¹H-NMR (400 MHz, CDCl3): δ 10.06 (s,1H), 8.02 (s, 1H), 7.94 (d, 2H), 7.78 (dd, 1H), 7.68 (m, 3H), 7.20 (m,1H), 7.94 (d, 1H), 7.10 (s, 1H), 6.96 (d, 1H), 3.96 (s, 3H), 3.93 (s,3H). Mass (m/z): 359 (M+1)+.

The final product BC-165 was then made as follows:

To 2-(3′,4′-dimethoxy-[1,1′-biphenyl]-4-yl)benzofuran-6-carbaldehyde(210.9 mg, 0.59 mmol) was added cyanoacetic acid (120 mg) and ammoniumacetate (135 mg). Acetic acid (5 mL) was added and the reaction mixturewas heated to reflux for 3 h, cooled to room temperature, added water(10 mL) and stirred 5 hr at room temperature. The solid was collected byfiltration, and then the solid washed with water (40 mL) and then withhexanes (40 mL). The solid was then dried under high vacuum at 60° C.overnight to afford2-cyano-3-(2-(3′,4′-dimethoxy-[1,1′-biphenyl]-4-yl)benzofuran-6-yl)acrylicacid (BC-165, 0.165 g, 66%). ¹H NMR (400 MHz, DMSO-d6): δ 8.44 (s, 1H),8.36 (s, 1H), 8.04 (d, 2H), 8.00 (d, 1H), 7.84 (d, 3H), 7.63 (s, 1H),7.39 (d, 2H), 7.06 (d, 1H), 3.87 (s, 3H), 3.80 (s, 3H). Mass (m/z): 424(M−−1).

Example 17 Synthesis of BC-1762-(4-(diphenylamino)phenyl)benzofuran-6-carboxylic acid (BC-176) wasSynthesized According to Synthetic Scheme V Synthetic Scheme V

First, the intermediate methyl 2-hydroxy-3-iodobenzoate was made:

A flask was fitted with a reflux condenser, flushed with nitrogen andcharged with anhydrous methanol (7.9 mL) and acetyl chloride (0.03 mL).After 10 minutes 2-hydroxy-3-iodobenzoic acid (1.05 g) was added. Thereaction was heated to reflux for 5.5 hours then cooled to roomtemperature. The methanol was removed under vacuum and the residue thenredissolved in ethyl acetate (50 mL). The ethyl acetate solution waswashed with saturated sodium bicarbonate (10 mL) and brine (10 mL),dried over magnesium sulfate, filtered and concentrated to afford methyl2-hydroxy-3-iodobenzoate (1.1 g). ¹H NMR (400 MHz, Chloroform-d) δ 7.74(d, 1H), 7.61 (d, 1H), 7.33 (dd, 1H), 5.45 (s, 1H), 3.90 (s, 3H).

The next intermediate, methyl2-(4-(diphenylamino)phenyl)benzofuran-6-carboxylate was made as follows:

To a 100 mL flask was added methyl 2-hydroxy-3-iodobenzoate (1.1 g),4-ethynyltriphenylamine (1.28 g), bis(triphenylphosphine)palladiumdichloride (0.083 g), and copper(I) iodide (0.068 g). The flask waspurged with nitrogen for 20 minutes. A solution of triethylamine (2.76mL) in anhydrous acetonitrile (19.8 mL) was degassed by bubblingnitrogen through for 20 minutes. The triethylamine solution was added tothe reaction flask and the reaction heated to 40° C. for 2.5 hours. Themixture was cooled to room temperature and water (15 mL) and brine (15mL) added. The mixture was stirred at room temperature for 1 hour. Thelayers were then separated and the aqueous layer extracted with ethylacetate (3×25 mL). The combined organic fractions were washed with 1MHCl and brine, dried over magnesium sulfate, filtered and concentrated.The residue was purified via chromatography on silica gel (elution with0 to 8% ethyl acetate in hexanes) to afford methyl2-(4-(diphenylamino)phenyl)benzofuran-6-carboxylate (1.5 g). ¹H NMR (400MHz, Chloroform-d) δ 8.17 (s, 1H), 7.93 (dd, 1H), 7.72 (d, 2H), 7.56 (d,1H), 7.29 (dd, 5H), 7.19-7.05 (m, 7H), 6.91 (d, 1H), 3.94 (s, 3H).

Final product BC-176 was then made as follows:

To a solution of methyl2-(4-(diphenylamino)phenyl)benzofuran-6-carboxylate (0.51 g) in THF (6.0mL) was added 1M LiOH solution (1.2 mL). The reaction was stirred atroom temperature for 40 min then heated to 40° C. for 2.5 hours. Thereaction was heated to reflux for 19 hours then 1M LiOH (4.8 mL) wasadded. After an additional 4.5 hours the reaction was cooled to roomtemperature and water (10 mL) added. The aqueous was acidified to pH=4with acetic acid, then extracted with ethyl acetate (3×20 mL). Thecombined organic fractions were dried over sodium sulfate, filtered, andconcentrated to afford2-(4-(diphenylamino)phenyl)benzofuran-6-carboxylic acid (BC-176, 0.49g). ¹H NMR (400 MHz, DMSO-d6) δ 12.88, (broad s, 1H), 8.04 (s, 1H),7.85-7.77 (m, 3H), 7.66 (d, 1H), 7.39-7.29 (m, 5H), 7.15-7.04 (m, 6H),7.04-6.96 (m, 2H). Mass (m/z): 406 (M+1)+.

Example 18 Synthesis of2-(4-(diphenylamino)phenyl)-N-hydroxybenzofuran-6-carboxamide (BC-177)

A suspension of 2-(4-(diphenylamino)phenyl)benzofuran-6-carboxylic acid(BC-176, 0.13 g) in anhydrous dichloromethane (3.1 mL) was cooled to 0°C. and oxalyl chloride (0.053 mL) added. N,N-dimethylformamide (0.001mL) was added and the reaction stirred at 0° C. for 10 min. The ice bathwas removed and the reaction stirred at room temperature for 3 hours.The reaction was concentrated and anhydrous toluene (3 mL) was added andthen removed in vacuo. Toluene (3 mL) was again added and removed invacuo. The residue was dissolved in anhydrous dichloromethane (3.1 mL)and cooled to 0° C. Triethylamine (0.22 mL) and hydroxylaminehydrochloride (0.044 g) were added and the reaction was allowed to warmto room temperature slowly overnight. Water (10 mL) and saturated sodiumbicarbonate (5 mL) were added and the aqueous extracted withdichloromethane (3×15 mL). The combined organic was washed with 1M HCl(10 mL), dried over sodium sulfate, filtered and concentrated. Theresidue was purified via chromatography on silica gel (elution with 0 to5% methanol in dichloromethane) to afford2-(4-(diphenylamino)phenyl)-N-hydroxybenzofuran-6-carboxamide (BC-177,0.11 g). 1H NMR (400 MHz, DMSO-d6) δ 11.20 (broad s, 1H), 9.05 (broad s,1H), 7.94 (d, 1H), 7.82 (d, 2H), 7.70-7.64 (m, 2H), 7.40-7.30 (m, 5H),7.14-7.07 (m, 6H), 7.03 (d, 2H). Mass (m/z): 421 (M+H).

Example 19 Solar Cells Made Using Solar Cell Dyes—Set 1

Fluorine-doped tin oxide (FTO) coated glasses were cut into 2 cm×2 cmsize and cleaned by washing with successive 1% aqueous Triton X-100solution, deionized (DI) water, and isopropanol. After drying at roomtemperature, the cleaned FTO glasses were treated with Corona discharge(˜13000V) for approximately 20 seconds on the conducting side. Anaqueous dispersion containing 20% by weight of TiO₂ (AEROXIDE® TiO₂ P25, particle size of 21±5 nm, Evonik Industries, Essen, Del.) and 5% byweight of poly(4-vinyl pyridine) was prepared and blade coated (6-8microns thick) on the FTO coated side of the glass. The coating area wastrimmed to 1.0 cm2. The TiO₂ coated anode was sintered at 450° C. for 30minutes, cooled to about 80° C. and dropped into a dye solutioncontaining 0.3 mM of selected dye and 0.3 mM chenodeoxycholic acid in1:1 acetonitrile/t-butanol (v/v) solvent mixture. The anodes were keptin dye solution overnight, rinsed with acetonitrile and air dried in thedark. The dye sensitized anode was sandwiched with electrochemicallydeposited PEDOT catalyst on a FTO coated glass slide using Surlyn(Meltonix 1170-60PF from Solaronix, Switzerland) hot melt adhesivewindow by hot pressing at 125° C. for 45 seconds. A copper redoxelectrolyte solution consisting of 200 mMbis(6,6′-dimethyl-2,2′-bipyridine) copper (I) bis(trifluorosulfon)imide,50 mM bis(6,6′-dimethyl-2,2′-bipyridine) copper (II)bis(trifluorosulfon)imide, 100 mM of lithium bis(trifluorosulfon)imideand 0.5 M 4-(t-butyl)pyridine in acetonitrile was injected between anodeand cathode using a pinhole on the cathode. The pinhole was sealed usinga surlyn/glass cover and a heat sealing process. A conductive silverpaint was applied on the contact areas of anode and cathode and dried toform an electrical contact. Two cells were fabricated for each dye(denoted as “cell 1” and “cell 2”). The photovoltaic performance of thefabricated cells were measured under AM 1.5 conditions (1.5 atm) at alight intensity of 97 mW/cm². The solar performance of fabricated solarcells was characterized using open circuit voltage (V_(oc) in mV), shortcircuit current density (J_(sc) in milliamperes/square centimeter), fillfactor and overall solar conversion efficiency (in %) and shown inTable 1. The fill factor (FF) is defined as the ratio of the maximumpower from the solar cell to the product of V_(oc) and J_(sc).

TABLE 1 Photovoltaic characteristics of set 1 dye sensitized solar cellsunder 1 sun (AM 1.5) irradiation conditions Solar dye used Cell SizeV_(oc) J_(sc) Efficiency in making cell (cm²) (mV) (mA/cm²) FF (%)BC-154 Cell 1 0.60 706.32 0.39 0.571 0.158 BC-154 Cell 2 0.60 820.220.32 0.499 0.132 WBI-PC-174 Cell 1 0.60 679.55 0.45 0.570 0.176WBI-PC-174 Cell 2 0.60 655.38 0.34 0.542 0.122 BC-175 Cell 1 0.50 916.414.59 0.499 2.111 BC-175 Cell 2 0.60 918.04 4.86 0.461 2.069 WBI-PC-64cell 1 0.60 975.64 7.54 0.438 3.241 WBI-PC-64 cell 2 0.60 987.07 7.110.434 3.061 WBI-PC-63 cell 1 0.60 1013.20 6.69 0.547 3.730 WBI-PC-63cell 2 0.60 1018.54 6.81 0.531 3.699

Example 20 Solar Cells Made Using Solar Cell Dyes—Set 2

Fluorine-doped tin oxide (FTO) coated glasses were cut into 2 cm×2 cmsize and cleaned by washing with successive 1% aqueous Triton X-100solution, deionized (DI) water, and isopropanol. After drying at roomtemperature, the cleaned FTO glasses were treated with Corona discharge(˜13000V) for approximately 20 seconds on the conducting side. Anaqueous dispersion containing 20% by weight of TiO₂ (AEROXIDE® TiO₂ P25, particle size of 21±5 nm, Evonik Industries, Essen, Del.) and 5% byweight of poly(4-vinyl pyridine) was prepared and blade coated (6-8microns thick) on the FTO coated side of the glass. The coating area wastrimmed to about 1.0 cm2. The TiO₂ coated anode was sintered at 450° C.for 30 minutes, cooled to about 80° C. and dropped into a dye solutioncontaining 0.3 mM of selected dye and 0.3 mM chenodeoxycholic acid in1:1 acetonitrile/t-butanol (v/v) solvent mixture. The anodes were keptin dye solution overnight, rinsed with acetonitrile and air dried in thedark. The dye sensitized anode was sandwiched with electrochemicallydeposited PEDOT catalyst on a FTO coated glass slide using Surlyn(Meltonix 1170-60PF from Solaronix, Switzerland) hot melt adhesivewindow by hot pressing at 125° C. for 45 seconds. A copper redoxelectrolyte solution consisting of 200 mMbis(6,6′-dimethyl-2,2′-bipyridine) copper (I) bis(trifluorosulfon)imide,50 mM bis(6,6′-dimethyl-2,2′-bipyridine) copper (II)bis(trifluorosulfon)imide, 100 mM of lithium bis(trifluorosulfon)imideand 0.5 M 4-(t-butyl)pyridine in acetonitrile was injected between anodeand cathode using a pinhole on the cathode. The pinhole was sealed usinga surlyn/glass cover and a heat sealing process. A conductive silverpaint was applied on the contact areas of anode and cathode and dried toform an electrical contact. Two cells were fabricated for each dye(denoted as “cell 1” and “cell 2”). The photovoltaic performance of thefabricated cells were measured under AM 1.5 (1.5 atm) conditions at alight intensity of 97 mW/cm². The solar performance of fabricated solarcells was characterized using open circuit voltage (V_(oc) in mV), shortcircuit current density (J_(sc) in milliamperes/square centimeter), fillfactor and overall solar conversion efficiency (in %) and shown in Table2. The fill factor (FF) is defined as the ratio of the maximum powerfrom the solar cell to the product of V_(oc) and J_(sc).

TABLE 2 Photovoltaic characteristics of set 2 dye sensitized solar cellsusing 6,6′-dimethyl-2,2′-bipyridine ligand based copper redoxelectrolyte under 1 sun (AM 1.5) irradiation conditions V_(oc) J_(sc)Dye (mV) (mA/cm²) FF Efficiency WBI-PC-63 cell 1 1013.32 6.29 0.5543.550 WBI-PC-63 cell 2 1043.88 7.89 0.569 4.708 WBI-PC-78 cell 1 943.794.42 0.588 2.466 WBI-PC-78 cell 2 953.73 4.57 0.579 2.537 WBI-PC-81 cell1 1021.75 6.26 0.572 3.673 WBI-PC-81 cell 2 992.13 7.11 0.574 4.066BC-146 cell 1 965.10 4.90 0.625 2.971 BC-146 cell 2 930.88 4.39 0.6302.589 BC148 cell 1 1005.13 5.47 0.596 3.291 BC148 cell 2 963.31 5.440.602 3.172 BC-149 cell 1 1035.33 6.46 0.573 3.850 BC-149 cell 2 1014.717.25 0.579 4.277 BC-166 cell 1 842.81 2.71 0.640 1.469 BC-166 cell 2847.97 2.69 0.618 1.414 BC-173 cell 1 890.33 4.49 0.614 2.465 BC-173cell 2 896.27 4.49 0.593 2.400

Example 21 Solar Cells Made Using Solar Cell Dyes—Set 3

Fluorine-doped tin oxide (FTO) coated glasses were cut into 2 cm×2 cmsize and cleaned by washing with successive 1% aqueous Triton X-100solution, deionized (DI) water, and isopropanol. After drying at roomtemperature, the cleaned FTO glasses were treated with Corona discharge(˜13000V) for approximately 20 seconds on the conducting side. Anaqueous dispersion containing 20% by weight of TiO₂ (AEROXIDE® TiO₂ P25, particle size of 21±5 nm, Evonik Industries, Essen, Del.) and 5% byweight of poly(4-vinyl pyridine) was prepared and blade coated (6-8microns thick) on the FTO coated side of the glass. The coating area wastrimmed to 1.0 cm2. The TiO₂ coated anode was sintered at 450° C. for 30minutes, cooled to about 80° C. and dropped into a dye solutioncontaining 0.3 mM of selected dye and 0.3 mM chenodeoxycholic acid in1:1 acetonitrile/t-butanol (v/v) solvent mixture. The anodes were keptin dye solution overnight, rinsed with acetonitrile and air dried in thedark. The dye sensitized anode was sandwiched with electrochemicallydeposited PEDOT catalyst on a FTO coated glass slide using Surlyn(Meltonix 1170-60PF from Solaronix, Switzerland) hot melt adhesivewindow by hot pressing at 125° C. for 45 seconds. A copper redoxelectrolyte solution consisting of 200 mMbis(2,9-dimethyl-1,10-phenanthroline) copper (I)bis(trifluorosulfon)imide, 50 mM bis(2,9-dimethyl-1,10-phenanthroline)copper (II) bis(trifluorosulfon)imide, 100 mM of lithiumbis(trifluorosulfon)imide and 0.5 M 4-(tertiarybutyl)pyridine inacetonitrile was injected between anode and cathode using a pinhole onthe cathode. The pinhole was sealed using a surlyn/glass cover and aheat sealing process. A conductive silver paint was applied on thecontact areas of anode and cathode and dried to form an electricalcontact. The photovoltaic performance of the fabricated cells weremeasured under AM 1.5 (1.5 atm) conditions at a light intensity of 97mW/cm2. The solar performance of fabricated solar cells wascharacterized using open circuit voltage (V_(oc) in mV), short circuitcurrent density (J_(sc) in milliamperes/square centimeter), fill factorand over all solar conversion efficiency (in %) and shown in Table 3.The fill factor (FF) is defined as the ratio of the maximum power fromthe solar cell to the product of V_(oc) and J_(sc).

TABLE 3 Photovoltaic characteristics of set 3 dye sensitized solar cellsusing 2,9-dimethyl-1,10-phenanthroline ligand based copper redoxelectrolyte under 1 sun (AM 1.5) irradiation conditions V_(oc) J_(sc)Dye (mV) (mA/cm²) FF Efficiency WBI-PC-63 1053.07 5.96 0.651 4.102WBI-PC-78 954.63 2.32 0.672 1.498 WBI-PC-81 1023.62 4.89 0.665 3.347BC-146 960.02 3.65 0.707 2.491 BC148 1035.40 5.62 0.675 3.945 BC-1491076.35 6.52 0.682 4.808 BC-166 872.23 1.55 0.653 0.888 BC-173 860.072.66 0.367 0.844

Example 22 Electrochemical Characterization of Solar Dyes

Fluorine-doped tin oxide (FTO) coated glasses were cut into 2 cm×2 cmsize and cleaned by washing with successive 1% aqueous Triton X-100solution, deionized (DI) water, and isopropanol. After drying at roomtemperature, the cleaned FTO glasses were treated with Corona discharge(˜13000V) for approximately 20 seconds on the conducting side. Anaqueous dispersion containing 20% by weight of TiO₂ (AEROXIDE® TiO₂ P25, particle size of 21±5 nm, Evonik Industries, Essen, Del.) and 5% byweight of poly(4-vinyl pyridine) was prepared and blade coated (6-8microns thick) on the FTO coated side of the glass. The coating area wastrimmed to about 1.0 cm². The TiO₂ coated anode was sintered at 450° C.for 30 minutes, cooled to about 80° C. and dropped into a dye solutioncontaining 0.3 mM of selected dye and 0.3 mM chenodeoxycholic acid in1:1 acetonitrile/t-butanol (v/v) solvent mixture. The anodes were keptin dye solution overnight, rinsed with acetonitrile and air dried in thedark. CV measurements were then performed using selected dye-sensitized,titanium dioxide-coated electrodes in a three-electrode configuration(using a Pt wire counter electrode and Ag/AgNO₃ reference electrode) in2 mM ferrocene and 100 mM tetrabutylammonium hexafluorophosphate(TBAHFP) in acetonitrile solution. The sweep rate used was 10 mV/s.Table 4 shows reduction, oxidation and redox potentials of the dyes.

TABLE 4 Redox potentials of selected dyes E_(ox) vs E_(red) vs E_(1/2)vs Dye Sample NHE in mV NHE in mV NHE in mV Commercial dye D35 1249 10161132 from Dyenamo Commercial dye XY1b 1393 963 1178 from Dyenamo BC-0641278 1106 1192 WBI-PC-078 1331 1063 1197 WBI-PC-081 1441 983 1212 BC-1461391 1083 1237 BC-148 1312 1009 1161 BC-149 1397 1086 1242 BC-164 12781106 1192 BC-173 1144 991 1068 BC-175 1201 1025 1113

Example 23 Absorption Characteristics of Selected Solar Dyes

Selected dyes were dissolved in tetrahydrofuran in known concentrations(5 to 20 μM) and their absorption profiles were measured from 300 to 800nm using a quartz cuvette with 1 cm path length using a UV-visiblespectrophotometer (Agilent Technologies, Cary 60 UV-vis). Table 5 showsabsorption maxima and molar extinction coefficients at the absorptionmaximum of selected dyes.

TABLE 5 Absorption maxima and molar extinction coefficients of dyesAbsorption Molar extinction MW maximum in coefficient Dye (g/mol) nmλ_(max) ϵ_(max) (M⁻¹ cm⁻¹) BOD-4 614.77 469 35148 Commerical Dye 863.11476 29737 D35 WBI-PC-78 558.62 434 30359 WBI-PC-81 406.43 455 26416BC-146 380.4 462 25148 BC-149 456.5 428 30303 BC-154 437.5 454 33866BC165 425.44 400 34979 BC-166 372.42 417 13996 BC169 374.4 415 29447BC172 387.44 421 14794 BC-173 360.41 448 35909 WBI-PC-174 551.73 43827363 BC-175 394.43 430 31059 Commercial Dyenamo (Stockholm, SE) dyestructures

1.-14. (canceled)
 15. A solar cell dye for use in a DSSC, wherein thesolar cell dye is a compound of formula I:

wherein R⁶ is selected from the group consisting of —NR³R⁴, —R³, —OR³and halo; R⁵ is —(CR═CR-)n(CR═CR²—)R¹; n is an integer from 0 to 10; R¹and R² are independently selected from the group consisting of —H, —CN,—COOR, CONHR, CON(H)OR, —SO₃R, —SO₂R —OSO₃R, —PO₃HR, and —OPO₃HR,further wherein at least one of R¹ and R² is not —H; each R isindependently selected from —H and C₁₋₆ linear or branched alkyl; and R³and R⁴ are independently selected from the group consisting of H,substituted or unsubstituted linear or branched C₁-C₁₀ alkyl,substituted or unsubstituted phenyl, substituted or unsubstituted C₆-C₁₀aryl, substituted or unsubstituted C₅-C₁₀ heteroaryl, substituted orunsubstituted C₅-C₁₀ cycloalkyl, and substituted or unsubstituted C₅-C₁₀heterocycloalkyl; or R³ and R⁴ attached to their N together form a ringthat is substituted or unsubstituted C₅-C₁₀ heterocycloalkyl, providedthat if n=0, and R³ and R⁴ are both: (a) H; (b) substituted orunsubstituted linear or branched C₁-C₁₀ alkyl; or (c) substituted orunsubstituted phenyl or C₆-C₁₀ aryl, then R¹ and R² are not bothselected from the group consisting of —H, —CN, —COOR, and —CONHR. 16.The dye of claim 15 having the formula II:


17. The dye of claim 15 having the formula III:


18. The dye of claim 15 having the formula IV:


19. The dye of claim 18 wherein R⁶ is —NR³R⁴.
 20. The dye of claim 19wherein R⁶ is selected from the group consisting of diethylamino,diphenylamino, methyl(phenyl)amino, cyclohexyl(methyl)amino,bis(4-methoxyphenyl)amino, bis(4-(tert-butyl)phenyl)amino,di(pyridin-2-yl)amino, di(pyridin-3-yl)amino, di(pyridin-4-yl)amino,piperidin-1-yl, 4-methylpiperazin-1-yl, 4-phenylpiperazin-1-yl,pyrrolidin-1-yl, and morpholino.
 21. The dye of claim 19, wherein R⁶ is—R³ or —OR³.
 22. The dye of claim 21 wherein R⁶ is selected from thegroup consisting of 3′,4′-dimethoxyphenyl, tert-butyl, phenyoxy, andmethoxy.
 23. The dye of claim 19 wherein R⁶ is halo.
 24. The dye ofclaim 23 wherein R⁶ is bromo.
 25. The dye of claim 19 wherein R³ and R⁴are substituted or unsubstituted phenyl.
 26. The dye of claim 18 whereinR¹ and R² together are —CN and —COOH.
 27. A dye sensitized solar cellcomprising the solar cell dye of claim
 15. 28. A method of making a DSSCcomprising the step of incorporating the solar cell dye of claim 15 intothe DSSC.